Pharmacotherapy for smoking cessation: effects by subgroup defined by genetically informed biomarkers

Ewoud Schuit; Orestis A. Panagiotou; Marcus R Munafò; Derrick A Bennett; Andrew W Bergen; Sean P David

doi:10.1002/14651858.CD011823.pub2

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Figure 1

Flow diagram of the search and study selection.

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Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each study.

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Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Analysis 1.1

Comparison 1 Active NRT vs placebo ‐ rs1051730 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 1.2

Comparison 1 Active NRT vs placebo ‐ rs1051730 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 2.1

Comparison 2 Active NRT vs placebo ‐ rs16969968 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 3.1

Comparison 3 Active NRT vs placebo ‐ rs16969968 ‐ non‐Hispanic black or African American, Outcome 1 Six‐Month Abstinence.

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Analysis 3.2

Comparison 3 Active NRT vs placebo ‐ rs16969968 ‐ non‐Hispanic black or African American, Outcome 2 End of Treatment.

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Analysis 4.1

Comparison 4 Active NRT vs placebo ‐ rs 588765 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 5.1

Comparison 5 Active NRT vs placebo ‐ rs2036527 ‐ non‐Hispanic black or African American, Outcome 1 Six‐Month Abstinence.

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Analysis 5.2

Comparison 5 Active NRT vs placebo ‐ rs2036527 ‐ non‐Hispanic black or African American, Outcome 2 End of Treatment.

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Analysis 6.1

Comparison 6 Active NRT vs placebo ‐ DRD4 (exon 3 48 bp) ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 6.2

Comparison 6 Active NRT vs placebo ‐ DRD4 (exon 3 48 bp) ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 7.1

Comparison 7 Active NRT vs placebo ‐ NMR ‐ non‐Hispanic black and white, Outcome 1 Six‐Month Abstinence.

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Analysis 7.2

Comparison 7 Active NRT vs placebo ‐ NMR ‐ non‐Hispanic black and white, Outcome 2 End of Treatment.

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Analysis 8.1

Comparison 8 Bupropion vs placebo ‐ rs1051730 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 8.2

Comparison 8 Bupropion vs placebo ‐ rs1051730 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 9.1

Comparison 9 Bupropion vs placebo ‐ rs1051730 ‐ non‐Hispanic black or African American, Outcome 1 Six‐Month Abstinence.

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Analysis 9.2

Comparison 9 Bupropion vs placebo ‐ rs1051730 ‐ non‐Hispanic black or African American, Outcome 2 End of Treatment.

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Analysis 10.1

Comparison 10 Bupropion vs placebo ‐ rs16969968 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 11.1

Comparison 11 Bupropion vs placebo ‐ rs16969968 ‐ non‐Hispanic black or African American, Outcome 1 Six‐Month Abstinence.

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Analysis 11.2

Comparison 11 Bupropion vs placebo ‐ rs16969968 ‐ non‐Hispanic black or African American, Outcome 2 End of Treatment.

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Analysis 12.1

Comparison 12 Bupropion vs placebo ‐ rs588765 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 12.2

Comparison 12 Bupropion vs placebo ‐ rs588765 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 13.1

Comparison 13 Bupropion vs placebo ‐ rs2036527 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 13.2

Comparison 13 Bupropion vs placebo ‐ rs2036527 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 14.1

Comparison 14 Bupropion vs placebo ‐ rs2036527 ‐ non‐Hispanic black or African American, Outcome 1 Six‐Month Abstinence.

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Analysis 14.2

Comparison 14 Bupropion vs placebo ‐ rs2036527 ‐ non‐Hispanic black or African American, Outcome 2 End of Treatment.

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Analysis 15.1

Comparison 15 Bupropion vs placebo ‐ rs3733829 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 15.2

Comparison 15 Bupropion vs placebo ‐ rs3733829 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 16.1

Comparison 16 Bupropion vs placebo ‐ rs3733829 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 17.1

Comparison 17 Bupropion vs placebo ‐ rs7937 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 18.1

Comparison 18 Bupropion vs placebo ‐ rs7937 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 19.1

Comparison 19 Bupropion vs placebo ‐ rs1329650 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 20.1

Comparison 20 Bupropion vs placebo ‐ rs1329650 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 21.1

Comparison 21 Bupropion vs placebo ‐ rs1028936 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 22.1

Comparison 22 Bupropion vs placebo ‐ rs1028936 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 23.1

Comparison 23 Bupropion vs placebo ‐ rs215605 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 24.1

Comparison 24 Bupropion vs placebo ‐ rs215605 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 25.1

Comparison 25 Bupropion + any NRT vs placebo ‐ rs1051730 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 26.1

Comparison 26 Bupropion + any NRT vs placebo ‐ rs1051730 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 27.1

Comparison 27 Bupropion + any NRT vs placebo ‐ rs16969968 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 28.1

Comparison 28 Bupropion + any NRT vs placebo ‐ rs16969968 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 29.1

Comparison 29 Bupropion + any NRT vs placebo ‐ rs2036527 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 30.1

Comparison 30 Bupropion + any NRT vs placebo ‐ rs2036527 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 31.1

Comparison 31 Bupropion + any NRT vs placebo ‐ rs3733829 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 32.1

Comparison 32 Bupropion + any NRT vs placebo ‐ rs3733829 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 33.1

Comparison 33 Bupropion + any NRT vs placebo ‐ rs7937 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 34.1

Comparison 34 Bupropion + any NRT vs placebo ‐ rs7937 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 35.1

Comparison 35 Bupropion + any NRT vs placebo ‐ rs1329650 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 36.1

Comparison 36 Bupropion + any NRT vs placebo ‐ rs1329650 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 37.1

Comparison 37 Bupropion + any NRT vs placebo ‐ rs1028936 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 38.1

Comparison 38 Bupropion + any NRT vs placebo ‐ rs1028936 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 39.1

Comparison 39 Bupropion + any NRT vs placebo ‐ rs215605 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 40.1

Comparison 40 Bupropion + any NRT vs placebo ‐ rs215605 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 41.1

Comparison 41 Bupropion + any NRT vs bupropion ‐ rs1051730 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 42.1

Comparison 42 Bupropion + any NRT vs bupropion ‐ rs1051730 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 43.1

Comparison 43 Bupropion + any NRT vs bupropion ‐ rs16969968 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 44.1

Comparison 44 Bupropion + any NRT vs bupropion ‐ rs16969968 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 45.1

Comparison 45 Bupropion + any NRT vs bupropion ‐ rs2036527 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 46.1

Comparison 46 Bupropion + any NRT vs bupropion ‐ rs2036527 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 47.1

Comparison 47 Bupropion + any NRT vs bupropion ‐ rs3733829 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 48.1

Comparison 48 Bupropion + any NRT vs bupropion ‐ rs3733829 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 49.1

Comparison 49 Bupropion + any NRT vs bupropion ‐ rs7937 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 50.1

Comparison 50 Bupropion + any NRT vs bupropion ‐ rs7937 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 51.1

Comparison 51 Bupropion + any NRT vs bupropion ‐ rs1329650 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 52.1

Comparison 52 Bupropion + any NRT vs bupropion ‐ rs1329650 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 53.1

Comparison 53 Bupropion + any NRT vs bupropion ‐ rs1028936 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 54.1

Comparison 54 Bupropion + any NRT vs bupropion ‐ rs1028936 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 55.1

Comparison 55 Bupropion + any NRT vs bupropion ‐ rs215605 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 56.1

Comparison 56 Bupropion + any NRT vs bupropion ‐ rs215605 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 57.1

Comparison 57 Active NRT ‐ rs1051730 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 57.2

Comparison 57 Active NRT ‐ rs1051730 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 58.1

Comparison 58 Active NRT ‐ rs1051730 ‐ non‐Hispanic black or African American, Outcome 1 Six‐Month Abstinence.

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Analysis 59.1

Comparison 59 Active NRT ‐ rs16969968 ‐ non‐Hispanic black or African American, Outcome 1 Six‐Month Abstinence.

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Analysis 59.2

Comparison 59 Active NRT ‐ rs16969968 ‐ non‐Hispanic black or African American, Outcome 2 End of Treatment.

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Analysis 60.1

Comparison 60 Active NRT ‐ rs588765 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 60.2

Comparison 60 Active NRT ‐ rs588765 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 61.1

Comparison 61 Active NRT ‐ rs2036527 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 61.2

Comparison 61 Active NRT ‐ rs2036527 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 62.1

Comparison 62 Active NRT ‐ rs2036527 ‐ non‐Hispanic black or African American, Outcome 1 Six‐Month Abstinence.

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Analysis 62.2

Comparison 62 Active NRT ‐ rs2036527 ‐ non‐Hispanic black or African American, Outcome 2 End of Treatment.

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Analysis 63.1

Comparison 63 Active NRT ‐ DRD‐4 (exon 3 48 bp) ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 63.2

Comparison 63 Active NRT ‐ DRD‐4 (exon 3 48 bp) ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 64.1

Comparison 64 Active NRT ‐ SLC6A4 (Promoter) ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 64.2

Comparison 64 Active NRT ‐ SLC6A4 (Promoter) ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 65.1

Comparison 65 Active NRT‐NMR ‐ non‐Hispanic white or black or African American, Outcome 1 Six‐Month Abstinence.

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Analysis 65.2

Comparison 65 Active NRT‐NMR ‐ non‐Hispanic white or black or African American, Outcome 2 End of Treatment.

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Analysis 66.1

Comparison 66 Bupropion ‐ rs1051730 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 66.2

Comparison 66 Bupropion ‐ rs1051730 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 67.1

Comparison 67 Bupropion ‐ rs1051730 ‐ non‐Hispanic black or African American, Outcome 1 Six‐Month Abstinence.

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Analysis 67.2

Comparison 67 Bupropion ‐ rs1051730 ‐ non‐Hispanic black or African American, Outcome 2 End of Treatment.

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Analysis 68.1

Comparison 68 Bupropion ‐ rs16969968 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 69.1

Comparison 69 Bupropion ‐ rs16969968 ‐ non‐Hispanic black or African American, Outcome 1 Six‐Month Abstinence.

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Analysis 69.2

Comparison 69 Bupropion ‐ rs16969968 ‐ non‐Hispanic black or African American, Outcome 2 End of Treatment.

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Analysis 70.1

Comparison 70 Bupropion ‐ rs588765 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 70.2

Comparison 70 Bupropion ‐ rs588765 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 71.1

Comparison 71 Bupropion ‐ rs2036527 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 71.2

Comparison 71 Bupropion ‐ rs2036527 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 72.1

Comparison 72 Bupropion ‐ rs2036527 ‐ non‐Hispanic black or African American, Outcome 1 Six‐Month Abstinence.

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Analysis 72.2

Comparison 72 Bupropion ‐ rs2036527 ‐ non‐Hispanic black or African American, Outcome 2 End of Treatment.

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Analysis 73.1

Comparison 73 Bupropion ‐ rs3733829 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 73.2

Comparison 73 Bupropion ‐ rs3733829 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 74.1

Comparison 74 Bupropion ‐ rs3733829 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 75.1

Comparison 75 Bupropion ‐ rs7937 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 76.1

Comparison 76 Bupropion ‐ rs7937 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 77.1

Comparison 77 Bupropion ‐ rs1329650 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 78.1

Comparison 78 Bupropion ‐ rs1329650 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 79.1

Comparison 79 Bupropion ‐ rs1028936 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 80.1

Comparison 80 Bupropion ‐ rs1028936 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 81.1

Comparison 81 Bupropion ‐ rs215605 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 82.1

Comparison 82 Bupropion ‐ rs215605 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 83.1

Comparison 83 Varenicline ‐ rs16969968 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 83.2

Comparison 83 Varenicline ‐ rs16969968 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 84.1

Comparison 84 Varenicline ‐ rs588765 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 84.2

Comparison 84 Varenicline ‐ rs588765 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 85.1

Comparison 85 Bupropion + any NRT ‐ rs1051730 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 86.1

Comparison 86 Bupropion + any NRT ‐ rs1051730 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 87.1

Comparison 87 Bupropion + any NRT ‐ rs16969968 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 88.1

Comparison 88 Bupropion + any NRT ‐ rs16969968 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 89.1

Comparison 89 Bupropion + any NRT ‐ rs2036527 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 90.1

Comparison 90 Bupropion + any NRT ‐ rs2036527 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 91.1

Comparison 91 Bupropion + any NRT ‐ rs3733829 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 92.1

Comparison 92 Bupropion + any NRT ‐ rs3733829 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 93.1

Comparison 93 Bupropion + any NRT ‐ rs7937 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 94.1

Comparison 94 Bupropion + any NRT ‐ rs7937 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 95.1

Comparison 95 Bupropion + any NRT ‐ rs1329650 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 96.1

Comparison 96 Bupropion + any NRT ‐ rs1329650 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 97.1

Comparison 97 Bupropion + any NRT ‐ rs1028936 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 98.1

Comparison 98 Bupropion + any NRT ‐ rs1028936 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 99.1

Comparison 99 Bupropion + any NRT ‐ rs215605 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 100.1

Comparison 100 Bupropion + any NRT ‐ rs215605 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 101.1

Comparison 101 Placebo ‐ rs1051730 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 101.2

Comparison 101 Placebo ‐ rs1051730 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 102.1

Comparison 102 Placebo ‐ rs1051730 ‐ non‐Hispanic black or African American, Outcome 1 Six‐Month Abstinence.

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Analysis 102.2

Comparison 102 Placebo ‐ rs1051730 ‐ non‐Hispanic black or African American, Outcome 2 End of Treatment.

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Analysis 103.1

Comparison 103 Placebo ‐ rs16969968 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 103.2

Comparison 103 Placebo ‐ rs16969968 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 104.1

Comparison 104 Placebo ‐ rs16969968 ‐ non‐Hispanic black or African American, Outcome 1 Six‐Month Abstinence.

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Analysis 104.2

Comparison 104 Placebo ‐ rs16969968 ‐ non‐Hispanic black or African American, Outcome 2 End of Treatment.

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Analysis 105.1

Comparison 105 Placebo ‐ rs588765 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 105.2

Comparison 105 Placebo ‐ rs588765 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 106.1

Comparison 106 Placebo ‐ rs588765 ‐ non‐Hispanic black or African American, Outcome 1 Six‐Month Abstinence.

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Analysis 106.2

Comparison 106 Placebo ‐ rs588765 ‐ non‐Hispanic black or African American, Outcome 2 End of Treatment.

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Analysis 107.1

Comparison 107 Placebo ‐ rs2036527 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 107.2

Comparison 107 Placebo ‐ rs2036527 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 108.1

Comparison 108 Placebo ‐ rs2036527 ‐ non‐Hispanic black or African American, Outcome 1 Six‐Month Abstinence.

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Analysis 108.2

Comparison 108 Placebo ‐ rs2036527 ‐ non‐Hispanic black or African American, Outcome 2 End of Treatment.

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Analysis 109.1

Comparison 109 Placebo ‐ DRD‐4 (exon 3 48 bp) ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 109.2

Comparison 109 Placebo ‐ DRD‐4 (exon 3 48 bp) ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 110.1

Comparison 110 Placebo ‐ rs3733829 ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 110.2

Comparison 110 Placebo ‐ rs3733829 ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 111.1

Comparison 111 Placebo ‐ rs7937 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 112.1

Comparison 112 Placebo ‐ rs7937 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 113.1

Comparison 113 Placebo ‐ rs1329650 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 114.1

Comparison 114 Placebo ‐ rs1329650 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 115.1

Comparison 115 Placebo ‐ rs1028936 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 116.1

Comparison 116 Placebo ‐ rs1028936 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 117.1

Comparison 117 Placebo ‐ rs215605 ‐ non‐Hispanic white, Outcome 1 End of Treatment.

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Analysis 118.1

Comparison 118 Placebo ‐ rs215605 ‐ non‐Hispanic black or African American, Outcome 1 End of Treatment.

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Analysis 119.1

Comparison 119 Placebo ‐ SLC6A4 (Promoter) ‐ non‐Hispanic white, Outcome 1 Six‐Month Abstinence.

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Analysis 119.2

Comparison 119 Placebo ‐ SLC6A4 (Promoter) ‐ non‐Hispanic white, Outcome 2 End of Treatment.

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Analysis 120.1

Comparison 120 Placebo ‐ NMR ‐ non‐Hispanic white or black or African American, Outcome 1 Six‐Month Abstinence.

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Analysis 120.2

Comparison 120 Placebo ‐ NMR ‐ non‐Hispanic white or black or African American, Outcome 2 End of Treatment.

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Summary of findings for the main comparison. Active NRT compared with placebo ‐ rs1051730 ‐ non‐Hispanic white for smoking cessation

Active NRT compared with placebo ‐ rs1051730 ‐ non‐Hispanic white for smoking cessation^a
Patient or population: people who smoke Setting: community and healthcare settings Intervention: active NRT Comparison: placebo
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with active NRT ‐ rs1051730 ‐ non‐Hispanic white	Risk with placebo
Abstinence at end of treatment	Study population		RR 1.63 (1.14 to 2.32)	1391 (2 RCTs)	⊕⊕⊕⊝ MODERATE^b,c	Pooled result across studies, including all genotypes. Between‐genotype group heterogeneity P value = 0.004 (see results for individual subgroups in below rows)
	327 per 1000 (228 to 465)	200 per 1000
Abstinence at end of treatment ‐ homozygous major	Study population		RR 1.09 (0.85 to 1.41)	582 (2 RCTs)	⊕⊕⊝⊝ LOW^c,d	For participants with homozygous major genotype, low‐quality evidence suggests no effect.
	286 per 1000 (223 to 370)	263 per 1000
Abstinence at end of treatment ‐ heterozygous	Study population		RR 2.13 (1.52 to 2.97)	631 (2 RCTs)	⊕⊕⊕⊝ MODERATE^c	For participants with heterozygous genotype, moderate‐quality evidence shows effect in favour intervention.
	335 per 1000 (239 to 467)	157 per 1000
Abstinence at end of treatment ‐ homozygous minor	Study population		RR 2.18 (1.04 to 4.58)	178 (2 RCTs)	⊕⊕⊝⊝ LOW^c,e	For participants with homozygous minor genotype, low‐quality evidence shows effect in favour intervention.
	338 per 1000 (161 to 710)	155 per 1000
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; NRT: nicotine replacement therapy; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aThis is the first of seven 'Summary of findings' tables for the main comparison. For a complete list, see the 'Additional summary of findings' section. ^bNot downgraded owing to inconsistency, as large statistical heterogeneity can be explained by differences between genotypes. ^cDowngraded one level owing to risk of bias: high potential for selection bias in GRPG 1993 due to low fraction of genotyped participants. ^dDowngraded one level owing to imprecision: optimal information size criterion is met, but 95% CIs include the null effect and fail to exclude important benefit or important harm. ^eDowngraded one level owing to imprecision: optimal information size criterion is not met in this stratum. Counts in this stratum are smaller than in a single adequately powered trial.

Summary of findings for the main comparison. Active NRT compared with placebo ‐ rs1051730 ‐ non‐Hispanic white for smoking cessation

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Summary of findings 2. Active NRT compared with placebo ‐ rs16969968 ‐ non‐Hispanic white for smoking cessation

Active NRT compared with placebo ‐ rs16969968 ‐ non‐Hispanic white for smoking cessation
Patient or population: people who smoke Setting: community and healthcare settings Intervention: active NRT Comparison: placebo
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with placebo ‐ rs16969968 ‐ non‐Hispanic white	Risk with active NRT
End of treatment	Study population		RR 1.38 (0.97 to 1.98)	1127 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a,b	Pooled result across studies, including all genotypes. Between‐genotype group heterogeneity P value = 0.03 (see results for individual subgroups in below rows)
	251 per 1000	346 per 1000 (243 to 496)
End of treatment ‐ homozygous major	Study population		RR 1.01 (0.77 to 1.33)	449 (2 RCTs)	⊕⊕⊝⊝ LOW^a,c	For participants with homozygous major genotype, low‐quality evidence suggests no effect.
	333 per 1000	337 per 1000 (257 to 443)
End of treatment ‐ heterozygous	Study population		RR 1.85 (1.33 to 2.59)	550 (2 RCTs)	⊕⊕⊕⊕ HIGH	For participants with heterozygous genotype, high‐quality evidence shows effect in favour of intervention.
	193 per 1000	358 per 1000 (257 to 501)
End of treatment ‐ homozygous minor	Study population		RR 1.80 (0.45 to 7.23)	128 (2 RCTs)	⊕⊕⊝⊝ LOW^d	For participants with homozygous minor genotype, low‐quality evidence shows that point estimate favours intervention, but 95% CI crosses null effect.
	233 per 1000	420 per 1000 (105 to 1000)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; NRT: nicotine replacement therapy; RCT, randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence. High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aDowngraded one level owing to imprecision: Optimal information size criterion is met, but 95% CIs include the null effect and fail to exclude important benefit or important harm. ^bNot downgraded owing to inconsistency, as large statistical heterogeneity can be explained by differences in genotypes. ^cDowngraded one level owing to inconsistency: unexplained heterogeneity. ^dDowngraded two levels owing to serious imprecision: optimal information size criterion not met, and 95% CIs include the null effect and fail to exclude important benefit or important harm.

Summary of findings 2. Active NRT compared with placebo ‐ rs16969968 ‐ non‐Hispanic white for smoking cessation

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Summary of findings 3. Active NRT compared with placebo ‐ rs16969968 ‐ non‐Hispanic black or African American for smoking cessation

Active NRT compared with placebo ‐ rs16969968 ‐ non‐Hispanic black or African American for smoking cessation
Patient or population: people who smoke Setting: community and healthcare settings Intervention: active NRT Comparison: placebo
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with active NRT ‐ rs16969968 ‐ non‐Hispanic black or African American	Risk with placebo
Abstinence at 6 months	Study population		RR 1.11 (0.55 to 2.26)	709 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a,b	Pooled result across studies, including all genotypes. Between‐genotype group heterogeneity P value = 0.03 (see results for individual subgroups in below rows)
	203 per 1000 (101 to 414)	183 per 1000
Abstinence at 6 months ‐ homozygous major	Study population		RR 1.47 (1.07 to 2.03)	637 (2 RCTs)	⊕⊕⊕⊕ HIGH	For participants with homozygous major genotype, high‐quality evidence shows effect in favour of intervention.
	254 per 1000 (185 to 350)	173 per 1000
Abstinence at 6 months ‐ heterozygous or homozygous minor	Study population		RR 0.43 (0.15 to 1.26)	72 (2 RCTs)	⊕⊕⊝⊝ LOW^c	For participants with heterozygous or homozygous minor genotype, point estimate favours control, but 95% CI crosses null effect.
	117 per 1000 (41 to 344)	273 per 1000
Abstinence at end of treatment	Study population		RR 1.03 (0.36 to 2.94)	709 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a,b	Pooled result across studies, including all genotypes. Between‐genotype group heterogeneity P value = 0.003 (see results for individual subgroups in below rows)
	201 per 1000 (70 to 575)	196 per 1000
Abstinence at end of treatment ‐ homozygous major	Study population		RR 1.57 (1.15 to 2.15)	637 (2 RCTs)	⊕⊕⊕⊕ HIGH	For participants with homozygous major genotype, high‐quality evidence shows effect in favour of intervention.
	276 per 1000 (202 to 379)	176 per 1000
Abstinence at end of treatment ‐ heterozygous or homozygous minor	Study population		RR 0.29 (0.10 to 0.86)	72 (2 RCTs)	⊕⊕⊕⊝ MODERATE^d	For participants with heterozygous or homozygous minor genotype, moderate‐quality evidence shows effect in favour of control.
	105 per 1000 (36 to 313)	364 per 1000
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; NRT: nicotine replacement therapy; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence. High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aNot downgraded owing to inconsistency, as large statistical heterogeneity can be explained by differences in genotypes. ^bDowngraded one level owing to imprecision: Optimal information size criterion is met, but 95% CIs include the null effect and fail to exclude important benefit or important harm. ^cDowngraded two levels owing to serious imprecision: optimal information size criterion not met, but 95% CIs include the null effect and fail to exclude important benefit or important harm. ^dDowngraded one level owing to imprecision: low number of events; optimal information size criterion not met.

Summary of findings 3. Active NRT compared with placebo ‐ rs16969968 ‐ non‐Hispanic black or African American for smoking cessation

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Summary of findings 4. Active NRT compared with placebo ‐ rs 588765 ‐ non‐Hispanic white for smoking cessation

Active NRT compared with placebo ‐ rs 588765 ‐ non‐Hispanic white for smoking cessation
Patient or population: people who smoke Setting: community and healthcare settings Intervention: active NRT Comparison: placebo
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with placebo ‐ rs 588765 ‐ non‐Hispanic white	Risk with active NRT
End of treatment	Study population		RR 1.33 (1.04 to 1.71)	923 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	Pooled result across studies, including all genotypes. Between‐genotype group heterogeneity P value = 0.92 (see results for individual subgroups in below rows)
	211 per 1000	281 per 1000 (220 to 361)
End of treatment ‐ homozygous major	Study population		RR 1.39 (0.89 to 2.16)	296 (2 RCTs)	⊕⊕⊝⊝ LOW^b	For participants with homozygous major genotype, low‐quality evidence suggests that point estimate favours intervention, but 95% CI crosses null effect.
	208 per 1000	288 per 1000 (185 to 448)
End of treatment ‐ heterozygous	Study population		RR 1.27 (0.89 to 1.79)	469 (2 RCTs)	⊕⊕⊝⊝ LOW^b	For participants with heterozygous genotype, point estimate favours intervention, but 95% CI crosses null effect.
	208 per 1000	265 per 1000 (185 to 373)
End of treatment ‐ homozygous minor	Study population		RR 1.50 (0.74 to 3.06)	158 (2 RCTs)	⊕⊕⊝⊝ LOW^b	For participants with homozygous minor genotype, low‐quality evidence suggests that point estimate favours intervention, but 95% CI crosses null effect.
	226 per 1000	339 per 1000 (167 to 691)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; NRT: nicotine replacement therapy; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence. High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aDowngraded one level owing to imprecision: low number of events; optimal information size criterion not met. ^bDowngraded two levels owing to serious imprecision: optimal information size criterion not met, but 95% CIs include the null effect and fail to exclude important benefit or important harm.

Summary of findings 4. Active NRT compared with placebo ‐ rs 588765 ‐ non‐Hispanic white for smoking cessation

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Summary of findings 5. Active NRT compared with placebo ‐ rs2036527 ‐ non‐Hispanic black or African American for smoking cessation

Active NRT compared with placebo ‐ rs2036527 ‐ non‐Hispanic black or African American for smoking cessation
Patient or population: people who smoke Setting: community and healthcare settings Intervention: active NRT Comparison: placebo
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with placebo ‐ rs2036527 ‐ non‐Hispanic black or African American	Risk with active NRT
6‐Month abstinence	Study population		RR 1.18 (0.75 to 1.87)	708 (2 RCTs)	⊕⊕⊝⊝ LOW^a	Pooled result across studies, including all genotypes. Between‐genotype group heterogeneity P value = 0.19 (see results for individual subgroups in below rows)
	177 per 1000	208 per 1000 (132 to 330)
6‐Month abstinence ‐ homozygous major	Study population		RR 1.95 (0.46 to 8.26)	425 (2 RCTs)	⊕⊝⊝⊝ VERY LOW^a,b	For participants with homozygous major genotype, very low‐quality evidence suggests that point estimate favours intervention, but 95% CI crosses null effect.
	171 per 1000	333 per 1000 (79 to 1000)
6‐Month abstinence ‐ heterozygous or homozygous minor	Study population		RR 0.90 (0.40 to 2.03)	283 (2 RCTs)	⊕⊕⊕⊝ MODERATE^c	For participants with heterozygous or homozygous minor genotype, moderate‐quality evidence shows no effect.
	185 per 1000	167 per 1000 (74 to 377)
End of treatment	Study population		RR 1.22 (0.77 to 1.93)	708 (2 RCTs)	⊕⊕⊝⊝ LOW^a	Pooled results across studies, including all genotypes. Between‐genotype group heterogeneity P value = 0.19 (see results for individual subgroups in below rows)
	199 per 1000	242 per 1000 (153 to 384)
End of treatment ‐ homozygous major	Study population		RR 2.39 (0.43 to 13.35)	425 (2 RCTs)	⊕⊕⊝⊝ LOW^b,c	For participants with homozygous major genotype, low‐quality evidence suggests that point estimate favours intervention, but 95% CI crosses null effect.
	197 per 1000	471 per 1000 (85 to 1000)
End of treatment ‐ heterozygous or homozygous minor	Study population		RR 0.89 (0.55 to 1.46)	283 (2 RCTs)	⊕⊕⊕⊝ MODERATE^c	For participants with heterozygous or homozygous minor genotype, moderate‐quality evidence shows no effect.
	202 per 1000	179 per 1000 (111 to 294)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; NRT: nicotine replacement therapy; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence. High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^cDowngraded one level owing to imprecision: low number of events; optimal information size criterion not met.

Summary of findings 5. Active NRT compared with placebo ‐ rs2036527 ‐ non‐Hispanic black or African American for smoking cessation

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Summary of findings 6. Active NRT compared with placebo ‐ DRD4 (exon 3 48 bp) ‐ non‐Hispanic white for smoking cessation

Active NRT compared with placebo ‐ DRD4 (exon 3 48 bp) ‐ non‐Hispanic white for smoking cessation
Patient or population: people who smoke Setting: community and healthcare settings Intervention: active NRT Comparison: placebo
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with placebo ‐ DRD4 (exon 3 48 bp) ‐ non‐Hispanic white	Risk with active NRT
6‐Month abstinence	Study population		RR 1.44 (1.08 to 1.92)	900 (2 RCTs)	⊕⊕⊝⊝ LOW^a,b	Pooled result across studies, including all genotypes. Between‐genotype group heterogeneity P value = 0.85 (see results for individual subgroups in below rows)
	141 per 1000	203 per 1000 (152 to 271)
6‐month abstinence ‐ homozygous major	Study population		RR 1.34 (0.93 to 1.93)	566 (2 RCTs)	⊕⊝⊝⊝ VERY LOW^a,b,c	For participants with homozygous major genotype, very low‐quality evidence suggests that point estimate favours intervention, but 95% CI crosses null effect.
	155 per 1000	207 per 1000 (144 to 299)
6‐Month abstinence ‐ heterozygous	Study population		RR 1.76 (1.00 to 3.10)	290 (2 RCTs)	⊕⊕⊝⊝ LOW^a,b	For participants with heterozygous genotype, low‐quality evidence suggests effect in favour of intervention.
	113 per 1000	198 per 1000 (113 to 349)
6‐Month abstinence ‐ homozygous minor	Study population		RR 1.28 (0.40 to 4.11)	44 (2 RCTs)	⊕⊝⊝⊝ VERY LOW^a,b,c	For participants with homozygous minor genotype, very low‐quality evidence suggests that point estimate favours intervention, but 95% CI crosses null effect.
	167 per 1000	213 per 1000 (67 to 685)
End of treatment	Study population		RR 1.20 (0.88 to 1.63)	900 (2 RCTs)	⊕⊕⊝⊝ LOW^a,b	Pooled result across studies, including all genotypes. Between‐genotype group heterogeneity P value = 0.78 (see results for individual subgroups in below rows)
	271 per 1000	325 per 1000 (238 to 441)
End of treatment ‐ homozygous major	Study population		RR 1.22 (0.59 to 2.51)	566 (2 RCTs)	⊕⊝⊝⊝ VERY LOW^a,b,c	For participants with homozygous major genotype, very low‐quality evidence suggests that point estimate favours intervention, but 95% CI crosses null effect.
	273 per 1000	334 per 1000 (161 to 686)
End of treatment ‐ heterozygous	Study population		RR 1.40 (0.57 to 3.39)	290 (2 RCTs)	⊕⊝⊝⊝ VERY LOW^a,b,c	For participants with heterozygous genotype, very low‐quality evidence suggests that point estimate favours intervention, but 95% CI crosses null effect.
	258 per 1000	362 per 1000 (147 to 876)
End of treatment ‐ homozygous minor	Study population		RR 1.02 (0.65 to 1.58)	44 (2 RCTs)	⊕⊕⊝⊝ LOW^a,b	For participants with homozygous minor genotype, low‐quality evidence suggests no effect.
	333 per 1000	340 per 1000 (217 to 527)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; NRT: nicotine replacement therapy; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence. High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aDowngraded one level owing to high risk of bias: high risk of selection bias in GRPG 1993 due to low fraction of genotyped participants. ^bDowngraded one level owing to imprecision: low number of events; optimal information size criterion not met. ^cDowngraded one level owing to imprecision: 95% CIs include the null effect and fail to exclude important benefit or important harm.

Summary of findings 6. Active NRT compared with placebo ‐ DRD4 (exon 3 48 bp) ‐ non‐Hispanic white for smoking cessation

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Summary of findings 7. Active NRT compared with placebo ‐ NMR ‐ non‐Hispanic black and white for smoking cessation

Active NRT compared with placebo ‐ NMR ‐ non‐Hispanic black and white for smoking cessation
Patient or population: people who smoke Setting: community and healthcare settings Intervention: active NRT Comparison: placebo
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with placebo ‐ NMR ‐ non‐Hispanic black and white	Risk with active NRT
6‐Month abstinence	Study population		RR 1.51 (1.08 to 2.10)	1417 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	Pooled result across studies, including all genotypes. Between‐genotype group heterogeneity: P value = 0.29 (see results for individual subgroups in below rows)
	99 per 1000	149 per 1000 (107 to 207)
6‐Month abstinence ‐ slow NMR	Study population		RR 1.82 (1.12 to 2.94)	628 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	For participants with slow NMR genotype, moderate‐quality evidence favours intervention.
	116 per 1000	211 per 1000 (130 to 341)
6‐Month abstinence ‐ normal NMR	Study population		RR 1.21 (0.78 to 1.87)	789 (2 RCTs)	⊕⊕⊝⊝ LOW^b	For participants with normal NMR genotype, point estimate favours intervention, but 95% CI crosses null effect.
	85 per 1000	103 per 1000 (66 to 159)
End of treatment	Study population		RR 1.51 (1.19 to 1.90)	1417 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	Pooled result across studies, including all genotypes. Between‐genotype group heterogeneity: P value = 0.52 (see results for individual subgroups in below rows)
	136 per 1000	205 per 1000 (162 to 258)
End of treatment ‐ slow NMR	Study population		RR 1.61 (1.18 to 2.20)	847 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	For participants with slow NMR genotype, moderate‐quality evidence favours intervention.
	127 per 1000	204 per 1000 (149 to 278)
End of treatment ‐ normal NMR	Study population		RR 1.49 (0.85 to 2.60)	570 (2 RCTs)	⊕⊕⊝⊝ LOW^a,b	For participants with normal NMR genotype, point estimate favours intervention, but 95% CI crosses null effect.
	149 per 1000	222 per 1000 (127 to 388)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; NMR: nicotine metabolite ratio; NRT: nicotine replacement therapy; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence. High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aDowngraded one level owing to risk of bias: 755/1532 (49%) participants from Patch Trial (GPRG 1993) were genotyped, which could contribute to selection bias. ^bDowngraded one level owing to imprecision: optimal information size criterion is met, but 95% CIs include the null effect and fail to exclude important benefit or important harm.

Summary of findings 7. Active NRT compared with placebo ‐ NMR ‐ non‐Hispanic black and white for smoking cessation

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Table 1. Glossary of genetic terms

Genetic term	Explanation
Single‐nucleotide polymorphism (SNP)	A single base pair change in the DNA sequence at a particular point compared with the “common” or “wild‐type” sequence (Attia 2009) Most common form of genetic variation in the genome, in which a single‐base substitution has created 2 forms of a DNA sequence that differ by a single nucleotide (Pearson 2008)
Alleles	Alternate forms of a gene or chromosomal locus that differ in DNA sequence (Pearson 2008)
Genome‐wide association study (GWAS)	Any study of genetic variation across the entire human genome designed to identify genetic association with observable traits or the presence or absence of a disease, usually referring to studies with genetic marker density of 100,000 or more to represent a large proportion of variation in the human genome (Pearson 2008)
Genotype	The genetic constitution of an individual, either overall or at a specific gene (Attia 2009)
Hardy‐Weinberg equilibrium (HWE)	Population distribution of 2 alleles (with frequencies p and q) such that the distribution is stable from generation to generation and genotypes occur at frequencies of p2, 2pq, and q2 for the major allele homozygote, heterozygote, and minor allele homozygote, respectively (Pearson 2008)
Linkage disequilibrium	Measure of association between 2 alleles located near each other on a chromosome, such that they are inherited together more frequently than would be expected by chance (Pearson 2008)
Loci	The site(s) on a chromosome at which the gene for a particular trait is located on a gene at which a particular SNP is located (Attia 2009)
Minor allele	The allele of a biallelic polymorphism that is less frequent in the study population (Pearson 2008)
Major allele	The allele of a biallelic polymorphism that is more frequent in the study population (Pearson 2008)
Pharmacogenetics	The field of studying the genetic basis of drug response and applying this knowledge to clinical practice by guiding drug prescribing
Pharmacogenomics	Similar to pharmacogenetics but uses information across the whole genome
Population stratification	A form of confounding in genetic association studies caused by genetic differences between cases and controls unrelated to disease but due to sampling from populations of different ancestries (Pearson 2008)
Wild‐type allele	The allele at a particular single‐nucleotide polymorphism (SNP) that is most frequent in a population, also called “common” allele (Attia 2009)
DNA = deoxyribonucleic acid; SNP = Single‐nucleotide polymorphism; GWAS = Genome‐wide association study; HWE = Hardy‐Weinberg equilibrium

Table 1. Glossary of genetic terms

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Table 2. Polymorphisms of interest, together with their major/minor alleles, stratified by race

Polymorphism		Race group
Gene/Region	SNP or VNTR^a	White^b	Black or African American^c	East Asian^d	Mexican^e
CHRNA3	rs1051730	G/A	G/A	G/A	G/A
CHRNA5	rs16969968	G/A	G/A	G/A	G/A
CHRNA5	rs588765	C/T	C/T	C/T	C/T
CHRNA5	rs2036527	G/A	G/A	G/A	G/A
CHRNB3	rs13280604	A/G	G/A	A/G	A/G
CYP2A6	rs4105144	T/C	T/C	T/C	T/C
CYP2B6	rs6474412	T/C	C/T	T/C	T/C
DBH	rs3025343	G/A	G/A	G/A	G/A
DRD4 (exon 3 48 bp)	SI000224I	4 (0.65), 7 (0.18), 3, 2	4 (0.75), 7 (0.14), 6, 5	4 (0.79), 2 (0.17), 5	7 (0.52), 4 (0.41), 2
EGLN2	rs3733829	A/G	A/G	A/G	G/A
EGLN2	rs7937	T/C	C/T	T/C	T/C
LOC100188947	rs1329650	G/T	G/T	T/G	G/T
LOC100188947	rs1028936	A/C	A/C	C/A	A/C
PDE1C	rs215605	T/G	G/T	G/T	T/G
SLC6A3 (3' 40 bp)	SI000156M	10 (0.69), 9 (0.31)	10 (0.73), 9 (0.21), 3, 8	10 (0.91), 9	10 (0.74), 9 (0.24)
SLC6A4 (Promoter)	SI664268G^f	L (0.62), S (0.38)	L (0.78), S (0.07), 19 (0.15)	L (0.27), S (0.71)	L (0.42), S (0.58)
^aSNP rsID and frequencies from the 1000 Genomes Project database (http://analysistools.nci.nih.gov/LDlink/), VNTR UID and frequencies from ALFRED (http://alfred.med.yale.edu/alfred/index.asp).
^bGBR or European (PopID = 20, SampID = 20C).
^cASW or per VNTR (DRD4, Biaka (PopID = 5, SampID = 5F); SLC6A3, African American (PopID = 98R, SampID = 101C); SLC6A4, Biaka.
^dCHB + JPT, or mean of Han and Japanese, for SLC6A3 and SLC6A4, Han (SampID = 9J) and Japanese (SampID = 10B).
^eMXL or per VNTR (DRD4, see Table 2, Aguirre‐Samudio 2014; SLC6A3, Hispanic American from ALFRED; SLC6A4, see Table 2, Peralta‐Leal 2012).
^fFor Euro, African American and East Asian, extracted from Promoter VNTR + rs25531 Table in ALFRED. L = 16 repeats, S = 14 repeats.
SNP = Single‐nucleotide polymorphism; VNTR = variable number tandem repeat; G = nucleobase guanine; A = nucleobase adenine; C = nucleobase cytosine; T = nucleobase thymine; rsID=reference SNP cluster ID; UID=Unique Identifier, from ALFRED; GBR=British in England and Scotland population description code from 1000 Genomes Project; PopID=Population ID from ALFRED; SampID=Sample ID from ALFRED; ASW=Americans of African Ancestry in SW USA population description code, from 1000 Genomes Project; CHB=Han Chinese in Bejing, China population description code, from 1000 Genomes Project; JPT=Japanese in Tokyo, Japan population description code, from 1000 Genomes Project; Han=Han Chinese living in the San Francisco, California, from ALFRED; MXL=Mexican Ancestry from Los Angeles USA population description code, from 1000 Genomes Project; L=Long (16 repeats); S=Short (14 repeats)

Table 2. Polymorphisms of interest, together with their major/minor alleles, stratified by race

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Table 3. Data availability per treatment comparison for the outcome 6‐month abstinence

Treatment comparison	SNP or VNTR^a	Ethnicity	Number of studies (individual treatment 1/treatment 2) included	Analysis number	Significant treatment effect Letter indicates which treatment is favoured: a = active NRT b = bupropion ba = bupropion + active NRT p = placebo v = varenicline				P value heterogeneity genotype groups
Active NRT vs placebo					O	HoMa	Het	HoMi
	rs1051730	NHW	3 (1023/574)	1.1	a		a	a	0.40
	rs16969968	NHB	2 (392/317)	3.1		a			0.03^a
	rs2036527	NHB	2 (391/317)	5.1					0.36^a
	DRD4 (exon 3 48 bp)	NHW	2 (453/447)	6.1	a		a		0.72
					O	S	N
	NMR	NHW or NHB	2 (719/699)	7.1	a	a			0.22
Bupropion vs placebo					O	HoMa	Het	HoMi
	rs1051730	NHW	4 (797/532)	8.1	b		b		0.77
		NHB	3 (63/63)	9.1					0.80
	rs16969968	NHB	2 (294/284)	11.1					0.22^a
	rs588765	NHW	4 (596/511)	12.1	b			b	0.32
	rs2036527	NHW	2 (412/326)	13.1	b			b	0.28
		NHB	3 (331/329)	14.1					0.65
	rs3733829	NHW	2 (307/264)	15.1	b		b		0.25
Het: heterozygous; HoMa: homozygous major; HoMi: homozygous minor; N: normal NMR; NHB: non‐Hispanic black or African American; NHW: non‐Hispanic white; NMR: nicotine metabolite ratio; NRT: nicotine replacement therapy; O = overall; SNP: single‐nucleotide polymorphism; VNTR: variable number tandem repeat. ^aHomozygous major vs heterozygous + homozygous minor.

Table 3. Data availability per treatment comparison for the outcome 6‐month abstinence

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Table 4. Data availability per treatment comparison for the outcome abstinence at end of treatment

Treatment comparison	SNP or VNTR^a	Ethnicity	Number of studies (individual treatment 1/treatment 2) included	Analysis number	Significant treatment effect Letter indicates which treatment is favoured: a = active NRT b = bupropion ba = bupropion + active NRT p = placebo v = varenicline				P value heterogeneity genotype groups
Active NRT vs placebo					O	HoMa	Het	HoMi
	rs1051730	NHW	2 (912/479)	1.2	a		a	a	0.004
	rs16969968	NHW	2 (784/343)	2.1			a		0.02
		NHB	2 (392/317)	3.2		a	p^b		0.003^a
	rs588765	NHW	2 (587/336)	4.1	a				0.89
	rs2036527	NHB	2 (391/317)	5.2					0.28^a
	DRD4 (exon 3 48 bp)	NHW	2 (453/447)	6.2					0.79
					O	S	N
	NMR	NHW or NHB	2 (718/699)	7.2	a	a			0.80
Bupropion vs placebo					O	HoMa	Het	HoMi
	rs1051730	NHW	6 (743/636)	8.2	b	b	b	b	0.41
		NHB	3 (84/75)	9.2					0.12
	rs16969968	NHW	3 (324/233)	10.1	b		b		0.50
		NHB	3 (315/296)	11.2	b		b^b		0.77^a
	rs588765	NHW	4 (595/512)	12.2	b	b			0.96
	rs2036527	NHW	4 (546/429)	13.2	b	b	b	b	0.20
		NHB	4 (352/341)	14.2	b	b			0.38
	rs3733829	NHW	4 (440/367)	15.2	b	b	b		0.71
		NHB	2 (46/29)	16.1					0.56^a
	rs7937	NHW	3 (324/233)	17.1	b	b			0.54
		NHB	2 (47/29)	18.1					0.92^a
	rs1329650	NHW	3 (324/235)	19.1	b	b			0.83
		NHB	2 (47/29)	20.1					0.59^a
	rs1028936	NHW	3 (324/235)	21.1	b	b			0.90
		NHB	2 (47/29)	22.1					0.37^a
	rs215605	NHW	3 (324/234)	23.1	b	b			0.43
		NHB	2 (47/29)	24.1					0.92^a
Bupropion + any NRT vs placebo					O	HoMa	Het	HoMi
	rs1051730	NHW	2 (268/176)	25.1	ba		ba		0.77
		NHB	2 (40/29)	26.1					0.07^a
	rs16969968	NHW	2 (266/175)	27.1	ba		ba		0.77
		NHB	2 (40/29)	28.1					0.35^a
	rs2036527	NHW	2 (267/176)	29.1	ba		ba		0.95
		NHB	2 (40/29)	30.1					0.59
	rs3733829	NHW	2 (266/175)	31.1	ba		ba		0.83
		NHB	2 (48/21[ES1] )	32.1					0.45^a
	rs7937	NHW	2 (268/174)	33.1	ba				0.62
		NHB	2 (40/29)	34.1					0.98^a
	rs1329650	NHW	2 (266/176)	35.1	ba	ba			0.90
		NHB	2 (40/29)	36.1					0.78^a
	rs1028936	NHW	2 (268/176)	37.1	ba	ba			0.88
		NHB	2 (40/29)	38.1					0.89^a
	rs215605	NHW	2 (267/175)	39.1	ba	ba			0.79
		NHB	2 (40/28)	40.1					0.52^a
Bupropion + any NRT vs bupropion					O	HoMa	Het	HoMi
	rs1051730	NHW	2 (268/265)	41.1					0.97
		NHB	2 (40/47)	42.1					0.41^a
	rs16969968	NHW	2 (266/265)	43.1					0.98
		NHB	2 (40/47)	44.1					0.57^a
	rs2036527	NHW	2 (267/265)	45.1					0.99
		NHB	2 (40/47)	46.1					0.61^a
	rs3733829	NHW	2 (267/264)	47.1					0.82
		NHB	2 (48/46)	48.1	b				0.58^a
	rs7937	NHW	2 (268/265)	49.1					0.69
		NHB	2 (40/47)	50.1					0.85^a
	rs1329650	NHW	2 (266/265)	51.1					0.66
		NHB	2 (40/47)	52.1					0.49^a
	rs1028936	NHW	2 (268/265)	53.1					0.60
		NHB	2 (40/47)	54.1					0.49^a
	rs215605	NHW	2 (267/265)	55.1					0.50
		NHB	2 (40/47)	56.1					0.75^a
Het: heterozygous; HoMa: homozygous major; HoMi: homozygous minor; N: normal NMR; NHB: non‐Hispanic black or African American; NHW: non‐Hispanic white; NMR: nicotine metabolite ratio; NRT: nicotine replacement therapy; O: overall; SNP: single‐nucleotide polymorphism; VNTR: variable number tandem repeat. ^aHomozygous major vs heterozygous + homozygous minor. ^bHeterozygous + homozygous minor.

Table 4. Data availability per treatment comparison for the outcome abstinence at end of treatment

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Table 5. Data availability per treatment group for the outcome 6‐month abstinence

Treatment group	SNP or VNTR^a	Ethnicity	Number of studies (individuals in homozygous major/heterozygous/homozygous minor) included	Analysis number	Significant treatment effect Letter indicates which genotype is favoured: ma = genotype group with 1 or more major alleles mi = homozygous minor s = slow NMR n = normal NMR		P value heterogeneity in genotype comparisons
Active NRT					MaMi	HetMi
	rs1051730	NHW	7 (1352/1025/310)	57.1			0.93
		NHB	2 (181/50/6)	58.1			0.98
	rs16969968	NHB	2 (353/39^a)	59.1			N/A
	rs588765	NHW	3 (286/399/147)	60.1			0.76
	rs2036527	NHW	2 (369/447/132)	61.1			0.79
		NHB	2 (232/159^a)	62.1			N/A
	DRD4 (exon 3 48 bp)	NHW	3 (798/253/68)	63.1			0.74
	SLC6A4 (Promoter)	NHW	2 (277/465/184)	64.1			0.62
					Normal vs slow
	NMR	NHW and NHB	2 (400/318)	65.1	s		N/A
Bupropion
	rs1051730	NHW	4 (220/294/96)	66.1			0.82
		NHB	2 (43/20^a)	67.1			N/A
	rs16969968	NHB	2 (261/33^a)	69.1			N/A
	rs588765	NHW	4 (195/292/109)	70.1			0.80
	rs2036527	NHW	2 (143/204/65)	71.1			0.87
		NHB	3 (187/144^a)	72.1			N/A
	rs3733829	NHW	2 (146/116/45)	73.1			0.65
Varenicline
	rs16969968	NHW	2 (269/349/89)	83.1			0.81
	rs588765	NHW	2 (234/345/120)	84.1			0.90
Placebo
	rs1051730	NHW	6 (377/441/156)	101.1			0.54
		NHB	2 (49/14^a)	102.1			N/A
	rs16969968	NHW	2 (132/181/30)	103.1			0.63
		NHB	3 (519/65^a)	104.1			N/A
	rs588765	NHW	5 (253/340/130)	105.1			0.92
		NHB	2 (275/291^a)	106.1			N/A
	rs2036527	NHW	2 (117/166/43)	107.1			0.81
		NHB	4 (373/256^a)	108.1			N/A
	DRD4 (exon 3 48 bp)	NHW	3 (361/186/26)	109.1			0.44
	rs3733829	NHW	2 (122/102/40)	110.1			0.60
	SLC6A4 (Promoter)	NHW	2 (128/23^a)	119.1			N/A
					Normal vs slow
	NMR	NHW and NHB	2 (389/310)	120.1			N/A
HetMi: heterozygous vs homozygous minor; MaMi: homozygous major vs homozygous minor; NHB: non‐Hispanic black or African American; NHW: non‐Hispanic white; NMR: nicotine metabolite ratio; NRT: nicotine replacement therapy; NS: normal NMR vs slow NMR; SNP: single‐nucleotide polymorphism; VNTR: variable number tandem repeat. ^aHeterozygous and homozygous minor combined.

Table 5. Data availability per treatment group for the outcome 6‐month abstinence

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Table 6. Data availability per treatment group for the outcome abstinence at end of treatment

Treatment group	SNP or VNTR^a	Ethnicity	Number of studies (individuals in homozygous major/heterozygous/homozygous minor) included	Analysis number	Significant treatment effect Letter indicates which genotype is favored: ma = genotype group with 1 or more major alleles mi = homozygous minor s = slow NMR n = normal NMR		P value heterogeneity in genotype comparisons
Active NRT					MaMi	HetMi
	rs1051730	NHW	5 (917/1008/283)	57.2			0.64
	rs16969968	NHB	2 (353/39^a)	59.2	ma^b		N/A
	rs588765	NHW	3 (286/399/147)	60.2			0.97
	rs2036527	NHW	2 (369/447/132)	61.2			0.74
		NHB	2 (232/159^a)	62.2	ma^b		N/A
	DRD4 (exon 3 48 bp)	NHW	3 (798/253/68)	63.2			0.72
	SLC6A4 (Promoter)	NHW	2 (277/465/184)	64.2			0.83
					Normal vs slow
	NMR	NHW and NHB	2 (400/318)	65.2			N/A
Bupropion
	rs1051730	NHW	6 (263/357/123)	66.2			0.59
		NHB	3 (58/26^a)	67.2			N/A
	rs16969968	NHW	3 (108/164/52)	68.1			0.51
		NHB	3 (279/36^a)	69.2			N/A
	rs588765	NHW	4 (195/292/109)	70.2			0.65
	rs2036527	NHW	4 (185/269/92)	71.2			0.53
		NHB	4 (200/152^a)	72.2			N/A
	rs3733829	NHW	4 (203/181/56)	73.2			0.87
		NHB	2 (35/11^a)	74.1			N/A
	rs7937	NHW	3 (86/165/73)	75.1			0.66
		NHB	2 (20/24/3)	76.1			0.62
	rs1329650	NHW	3 (161/138/25)	77.1			0.90
		NHB	2 (42/5^a)	78.1			N/A
	rs1028936	NHW	3 (212/103/9)	79.1			1.00
		NHB	2 (42/5^a)	80.1			N/A
	rs215605	NHW	3 (125/154/45)	81.1			0.94
		NHB	2 (31/16^a)	82.1			N/A
Varenicline
	rs16969968	NHW	2 (269/349/89)	83.2			0.94
	rs588765	NHW	2 (234/345/120)	84.2			0.84
Bupropion + any NRT
	rs1051730	NHW	2 (113/130/25)	85.1			0.96
		NHB	2 (33/7^a)	86.1			N/A
	rs16969968	NHW	2 (113/130/23)	87.1			0.98
		NHB	2 (36/4^a)	88.1			N/A
	rs2036527	NHW	2 (111/132/24)	89.1			0.82
		NHB	2 (23/12/5)	90.1			0.87
	rs3733829	NHW	2 (114/123/30)	91.1			0.52
		NHB	2 (30/10^a)	92.1	mi^b		N/A
	rs7937	NHW	2 (74/140/54)	93.1			0.95
		NHB	2 (13/27^a)	94.1			N/A
	rs1329650	NHW	2 (149/96/21)	95.1	mi		0.67
		NHB	2 (34/6^a)	96.1			N/A
	rs1028936	NHW	2 (183/75/10)	97.1			0.67
		NHB	2 (34/6^a)	98.1			N/A
	rs215605	NHW	2 (105/119/43)	99.1			0.25
		NHB	2 (18/22^a)	100.1
Placebo
	rs1051730	NHW	7 (378/441/164)	101.2			0.71
		NHB	3 (63/20^a)	102.2			N/A
	rs16969968	NHW	4 (169/227/49)	103.2			0.83
		NHB	4 (530/66^a)	104.2	mi^b		N/A
	rs588765	NHW	5 (254/296/108)	105.2			0.34
		NHB	2 (277/289^a)	106.2			N/A
	rs2036527	NHW	4 (154/213/62)	107.2			0.90
		NHB	5 (378/263^a)	108.2			N/A
	DRD4 (exon 3 48 bp)	NHW	3 (361/186/26)	109.2			0.65
	rs3733829	NHW	4 (164/152/51)	110.2			0.53
	rs7937	NHW	3 (73/120/40)	111.1			0.67
		NHB	2 (18/11^a)	112.1			N/A
	rs1329650	NHW	3 (119/106/10)	113.1			0.99
		NHB	2 (21/8^a)	114.1			N/A
	rs1028936	NHW	3 (158/72/5)	115.1			0.79
		NHB	2 (23/6^a)	116.1			N/A
	rs215605	NHW	3 (94/105/35)	117.1			0.70
		NHB	2 (18/11^a)	118.1			N/A
	SLC6A4 (Promoter)	NHW	2 (128/23^a)	119.2			N/A
					Normal vs slow
	NMR	NHW and NHB	2 (400/318)	120.2			N/A
HetMi: heterozygous vs homozygous minor; MaMi: homozygous major vs homozygous minor; NHB: non‐Hispanic black or African American; NHW: non‐Hispanic white; NS: normal NMR vs slow NMR; SNP: single‐nucleotide polymorphism; VNTR: variable number tandem repeat; NMR = nicotine metabolite ratio. ^aHeterozygous and homozygous minor combined. ^bHomozygous major vs heterozygous and homozygous minor.

Table 6. Data availability per treatment group for the outcome abstinence at end of treatment

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Comparison 1. Active NRT vs placebo ‐ rs1051730 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	3	1597	Risk Ratio (M‐H, Random, 95% CI)	1.42 [1.16, 1.75]

1.1 Homozygous Major	3	659	Risk Ratio (M‐H, Random, 95% CI)	1.27 [0.93, 1.72]
1.2 Heterozygous	3	731	Risk Ratio (M‐H, Random, 95% CI)	1.48 [1.08, 2.01]
1.3 Homozygous Minor	3	207	Risk Ratio (M‐H, Random, 95% CI)	2.07 [1.06, 4.01]
2 End of Treatment Show forest plot	2	1391	Risk Ratio (M‐H, Random, 95% CI)	1.63 [1.14, 2.32]

2.1 Homozygous Major	2	582	Risk Ratio (M‐H, Random, 95% CI)	1.09 [0.85, 1.41]
2.2 Heterozygous	2	631	Risk Ratio (M‐H, Random, 95% CI)	2.13 [1.52, 2.97]
2.3 Homozygous Minor	2	178	Risk Ratio (M‐H, Random, 95% CI)	2.18 [1.04, 4.58]

Comparison 1. Active NRT vs placebo ‐ rs1051730 ‐ non‐Hispanic white

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Comparison 2. Active NRT vs placebo ‐ rs16969968 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	1127	Risk Ratio (M‐H, Random, 95% CI)	1.38 [0.97, 1.98]

1.1 Homozygous Major	2	449	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.77, 1.33]
1.2 Heterozygous	2	550	Risk Ratio (M‐H, Random, 95% CI)	1.85 [1.33, 2.59]
1.3 Homozygous Minor	2	128	Risk Ratio (M‐H, Random, 95% CI)	1.80 [0.45, 7.23]

Comparison 2. Active NRT vs placebo ‐ rs16969968 ‐ non‐Hispanic white

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Comparison 3. Active NRT vs placebo ‐ rs16969968 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2	709	Risk Ratio (M‐H, Random, 95% CI)	1.11 [0.55, 2.26]

1.1 Homozygous Major	2	637	Risk Ratio (M‐H, Random, 95% CI)	1.47 [1.07, 2.03]
1.2 Heterozygous or Homozygous Minor	2	72	Risk Ratio (M‐H, Random, 95% CI)	0.43 [0.15, 1.26]
2 End of Treatment Show forest plot	2	709	Risk Ratio (M‐H, Random, 95% CI)	1.03 [0.36, 2.94]

2.1 Homozygous Major	2	637	Risk Ratio (M‐H, Random, 95% CI)	1.57 [1.15, 2.15]
2.2 Heterozygous or Homozygous Minor	2	72	Risk Ratio (M‐H, Random, 95% CI)	0.29 [0.10, 0.86]

Comparison 3. Active NRT vs placebo ‐ rs16969968 ‐ non‐Hispanic black or African American

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Comparison 4. Active NRT vs placebo ‐ rs 588765 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	923	Risk Ratio (M‐H, Random, 95% CI)	1.33 [1.04, 1.71]

1.1 Homozygous Major	2	296	Risk Ratio (M‐H, Random, 95% CI)	1.39 [0.89, 2.16]
1.2 Heterozygous	2	469	Risk Ratio (M‐H, Random, 95% CI)	1.27 [0.89, 1.79]
1.3 Homozygous Minor	2	158	Risk Ratio (M‐H, Random, 95% CI)	1.50 [0.74, 3.06]

Comparison 4. Active NRT vs placebo ‐ rs 588765 ‐ non‐Hispanic white

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Comparison 5. Active NRT vs placebo ‐ rs2036527 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2	708	Risk Ratio (M‐H, Random, 95% CI)	1.18 [0.75, 1.87]

1.1 Homozygous Major	2	425	Risk Ratio (M‐H, Random, 95% CI)	1.95 [0.46, 8.26]
1.2 Heterozygous or Homozygous Minor	2	283	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.40, 2.03]
2 End of Treatment Show forest plot	2	708	Risk Ratio (M‐H, Random, 95% CI)	1.22 [0.77, 1.93]

2.1 Homozygous Major	2	425	Risk Ratio (M‐H, Random, 95% CI)	2.39 [0.43, 13.35]
2.2 Heterozygous or Homozygous Minor	2	283	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.55, 1.46]

Comparison 5. Active NRT vs placebo ‐ rs2036527 ‐ non‐Hispanic black or African American

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Comparison 6. Active NRT vs placebo ‐ DRD4 (exon 3 48 bp) ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2	900	Risk Ratio (M‐H, Random, 95% CI)	1.44 [1.08, 1.92]

1.1 Homozygous Major	2	566	Risk Ratio (M‐H, Random, 95% CI)	1.34 [0.93, 1.93]
1.2 Heterozygous	2	290	Risk Ratio (M‐H, Random, 95% CI)	1.76 [1.00, 3.10]
1.3 Homozygous Minor	2	44	Risk Ratio (M‐H, Random, 95% CI)	1.28 [0.40, 4.11]
2 End of Treatment Show forest plot	2	900	Risk Ratio (M‐H, Random, 95% CI)	1.20 [0.88, 1.63]

2.1 Homozygous Major	2	566	Risk Ratio (M‐H, Random, 95% CI)	1.22 [0.59, 2.51]
2.2 Heterozygous	2	290	Risk Ratio (M‐H, Random, 95% CI)	1.40 [0.57, 3.39]
2.3 Homozygous Minor	2	44	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.65, 1.58]

Comparison 6. Active NRT vs placebo ‐ DRD4 (exon 3 48 bp) ‐ non‐Hispanic white

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Comparison 7. Active NRT vs placebo ‐ NMR ‐ non‐Hispanic black and white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2	1417	Risk Ratio (M‐H, Random, 95% CI)	1.51 [1.08, 2.10]

1.1 Slow NMR	2	628	Risk Ratio (M‐H, Random, 95% CI)	1.82 [1.12, 2.94]
1.2 Normal NMR	2	789	Risk Ratio (M‐H, Random, 95% CI)	1.21 [0.78, 1.87]
2 End of Treatment Show forest plot	2	1417	Risk Ratio (M‐H, Random, 95% CI)	1.51 [1.19, 1.90]

2.1 Slow NMR	2	847	Risk Ratio (M‐H, Random, 95% CI)	1.61 [1.18, 2.20]
2.2 Normal NMR	2	570	Risk Ratio (M‐H, Random, 95% CI)	1.49 [0.85, 2.60]

Comparison 7. Active NRT vs placebo ‐ NMR ‐ non‐Hispanic black and white

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Comparison 8. Bupropion vs placebo ‐ rs1051730 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	4	1329	Risk Ratio (M‐H, Random, 95% CI)	1.34 [1.11, 1.61]

1.1 Homozygous Major	4	495	Risk Ratio (M‐H, Random, 95% CI)	1.24 [0.94, 1.65]
1.2 Heterozygous	4	633	Risk Ratio (M‐H, Random, 95% CI)	1.44 [1.09, 1.91]
1.3 Homozygous Minor	4	201	Risk Ratio (M‐H, Random, 95% CI)	1.31 [0.57, 2.99]
2 End of Treatment Show forest plot	6	1379	Risk Ratio (M‐H, Random, 95% CI)	1.40 [1.19, 1.64]

2.1 Homozygous Major	6	496	Risk Ratio (M‐H, Random, 95% CI)	1.32 [1.05, 1.67]
2.2 Heterozygous	6	655	Risk Ratio (M‐H, Random, 95% CI)	1.36 [1.03, 1.79]
2.3 Homozygous Minor	6	228	Risk Ratio (M‐H, Random, 95% CI)	1.83 [1.20, 2.79]

Comparison 8. Bupropion vs placebo ‐ rs1051730 ‐ non‐Hispanic white

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Comparison 9. Bupropion vs placebo ‐ rs1051730 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2	124	Risk Ratio (M‐H, Random, 95% CI)	1.50 [0.75, 3.00]

1.1 Homozygous Major	2	92	Risk Ratio (M‐H, Random, 95% CI)	1.61 [0.71, 3.64]
1.2 Heterozygous	2	32	Risk Ratio (M‐H, Random, 95% CI)	1.30 [0.32, 5.34]
2 End of Treatment Show forest plot	3	157	Risk Ratio (M‐H, Random, 95% CI)	1.20 [0.70, 2.06]

2.1 Homozygous Major	3	117	Risk Ratio (M‐H, Random, 95% CI)	1.76 [0.96, 3.23]
2.2 Heterozygous	3	40	Risk Ratio (M‐H, Random, 95% CI)	0.68 [0.32, 1.44]

Comparison 9. Bupropion vs placebo ‐ rs1051730 ‐ non‐Hispanic black or African American

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Comparison 10. Bupropion vs placebo ‐ rs16969968 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	3	557	Risk Ratio (M‐H, Random, 95% CI)	1.42 [1.13, 1.77]

1.1 Homozygous Major	3	198	Risk Ratio (M‐H, Random, 95% CI)	1.35 [0.92, 1.99]
1.2 Heterozygous	3	276	Risk Ratio (M‐H, Random, 95% CI)	1.46 [1.04, 2.04]
1.3 Homozygous Minor	3	83	Risk Ratio (M‐H, Random, 95% CI)	2.55 [0.95, 6.85]

Comparison 10. Bupropion vs placebo ‐ rs16969968 ‐ non‐Hispanic white

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Comparison 11. Bupropion vs placebo ‐ rs16969968 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2	578	Risk Ratio (M‐H, Random, 95% CI)	1.30 [0.84, 2.00]

1.1 Homozygous Major	2	512	Risk Ratio (M‐H, Random, 95% CI)	1.18 [0.75, 1.87]
1.2 Heterozygous or Homozygous Minor	2	66	Risk Ratio (M‐H, Random, 95% CI)	2.82 [0.76, 10.45]
2 End of Treatment Show forest plot	3	611	Risk Ratio (M‐H, Random, 95% CI)	1.95 [1.23, 3.08]

2.1 Homozygous Major	3	541	Risk Ratio (M‐H, Random, 95% CI)	2.12 [1.44, 3.10]
2.2 Heterozygous or Homozygous Minor	3	70	Risk Ratio (M‐H, Random, 95% CI)	1.65 [0.33, 8.36]

Comparison 11. Bupropion vs placebo ‐ rs16969968 ‐ non‐Hispanic black or African American

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Comparison 12. Bupropion vs placebo ‐ rs588765 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	4	1107	Risk Ratio (M‐H, Random, 95% CI)	1.37 [1.12, 1.67]

1.1 Homozygous Major	4	384	Risk Ratio (M‐H, Random, 95% CI)	1.33 [0.85, 2.08]
1.2 Heterozygous	4	526	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.95, 1.65]
1.3 Homozygous Minor	4	197	Risk Ratio (M‐H, Random, 95% CI)	1.95 [1.18, 3.22]
2 End of Treatment Show forest plot	4	1107	Risk Ratio (M‐H, Random, 95% CI)	1.36 [1.13, 1.65]

2.1 Homozygous Major	4	385	Risk Ratio (M‐H, Random, 95% CI)	1.37 [1.05, 1.79]
2.2 Heterozygous	4	525	Risk Ratio (M‐H, Random, 95% CI)	1.31 [0.86, 2.01]
2.3 Homozygous Minor	4	197	Risk Ratio (M‐H, Random, 95% CI)	1.43 [0.99, 2.06]

Comparison 12. Bupropion vs placebo ‐ rs588765 ‐ non‐Hispanic white

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Comparison 13. Bupropion vs placebo ‐ rs2036527 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2	738	Risk Ratio (M‐H, Random, 95% CI)	1.40 [1.05, 1.86]

1.1 Homozygous Major	2	260	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.73, 1.80]
1.2 Heterozygous	2	370	Risk Ratio (M‐H, Random, 95% CI)	1.43 [0.99, 2.06]
1.3 Homozygous Minor	2	108	Risk Ratio (M‐H, Random, 95% CI)	2.73 [1.02, 7.36]
2 End of Treatment Show forest plot	4	975	Risk Ratio (M‐H, Random, 95% CI)	1.43 [1.19, 1.73]

2.1 Homozygous Major	4	339	Risk Ratio (M‐H, Random, 95% CI)	1.37 [1.04, 1.80]
2.2 Heterozygous	4	482	Risk Ratio (M‐H, Random, 95% CI)	1.36 [1.04, 1.79]
2.3 Homozygous Minor	4	154	Risk Ratio (M‐H, Random, 95% CI)	2.64 [1.33, 5.25]

Comparison 13. Bupropion vs placebo ‐ rs2036527 ‐ non‐Hispanic white

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Comparison 14. Bupropion vs placebo ‐ rs2036527 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	3	660	Risk Ratio (M‐H, Random, 95% CI)	1.30 [0.88, 1.92]

1.1 Homozygous Major	3	377	Risk Ratio (M‐H, Random, 95% CI)	1.17 [0.70, 1.98]
1.2 Heterozygous or Homozygous Minor	3	283	Risk Ratio (M‐H, Random, 95% CI)	1.44 [0.71, 2.91]
2 End of Treatment Show forest plot	4	693	Risk Ratio (M‐H, Random, 95% CI)	1.87 [1.36, 2.56]

2.1 Homozygous Major	4	395	Risk Ratio (M‐H, Random, 95% CI)	2.11 [1.39, 3.22]
2.2 Heterozygous or Homozygous Minor	4	298	Risk Ratio (M‐H, Random, 95% CI)	1.57 [0.93, 2.62]

Comparison 14. Bupropion vs placebo ‐ rs2036527 ‐ non‐Hispanic black or African American

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Comparison 15. Bupropion vs placebo ‐ rs3733829 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2	571	Risk Ratio (M‐H, Random, 95% CI)	1.41 [1.07, 1.87]

1.1 Homozygous Major	2	268	Risk Ratio (M‐H, Random, 95% CI)	1.21 [0.81, 1.82]
1.2 Heterozygous	2	218	Risk Ratio (M‐H, Random, 95% CI)	1.95 [1.22, 3.13]
1.3 Homozygous Minor	2	85	Risk Ratio (M‐H, Random, 95% CI)	1.13 [0.58, 2.17]
2 End of Treatment Show forest plot	4	807	Risk Ratio (M‐H, Random, 95% CI)	1.55 [1.29, 1.87]

2.1 Homozygous Major	4	367	Risk Ratio (M‐H, Random, 95% CI)	1.44 [1.11, 1.86]
2.2 Heterozygous	4	333	Risk Ratio (M‐H, Random, 95% CI)	1.69 [1.24, 2.30]
2.3 Homozygous Minor	4	107	Risk Ratio (M‐H, Random, 95% CI)	1.69 [0.96, 2.95]

Comparison 15. Bupropion vs placebo ‐ rs3733829 ‐ non‐Hispanic white

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Comparison 16. Bupropion vs placebo ‐ rs3733829 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	61	Risk Ratio (M‐H, Random, 95% CI)	1.51 [0.75, 3.04]

1.1 Homozygous Major	2	61	Risk Ratio (M‐H, Random, 95% CI)	1.51 [0.75, 3.04]

Comparison 16. Bupropion vs placebo ‐ rs3733829 ‐ non‐Hispanic black or African American

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Comparison 17. Bupropion vs placebo ‐ rs7937 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	3	557	Risk Ratio (M‐H, Random, 95% CI)	1.42 [1.13, 1.78]

1.1 Homozygous Major	3	159	Risk Ratio (M‐H, Random, 95% CI)	1.76 [1.13, 2.75]
1.2 Heterozygous	3	285	Risk Ratio (M‐H, Random, 95% CI)	1.30 [0.95, 1.76]
1.3 Homozygous Minor	3	113	Risk Ratio (M‐H, Random, 95% CI)	1.38 [0.82, 2.31]

Comparison 17. Bupropion vs placebo ‐ rs7937 ‐ non‐Hispanic white

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Comparison 18. Bupropion vs placebo ‐ rs7937 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	76	Risk Ratio (M‐H, Random, 95% CI)	1.56 [0.77, 3.18]

1.1 Homozygous Major	2	38	Risk Ratio (M‐H, Random, 95% CI)	1.70 [0.57, 5.10]
1.2 Heterozygous or Homozygous Minor	2	38	Risk Ratio (M‐H, Random, 95% CI)	1.57 [0.42, 5.84]

Comparison 18. Bupropion vs placebo ‐ rs7937 ‐ non‐Hispanic black or African American

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Comparison 19. Bupropion vs placebo ‐ rs1329650 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	3	559	Risk Ratio (M‐H, Random, 95% CI)	1.37 [1.07, 1.74]

1.1 Homozygous Major	3	280	Risk Ratio (M‐H, Random, 95% CI)	1.54 [1.07, 2.22]
1.2 Heterozygous	3	244	Risk Ratio (M‐H, Random, 95% CI)	1.31 [0.88, 1.96]
1.3 Homozygous Minor	3	35	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.33, 4.74]

Comparison 19. Bupropion vs placebo ‐ rs1329650 ‐ non‐Hispanic white

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Comparison 20. Bupropion vs placebo ‐ rs1329650 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	76	Risk Ratio (M‐H, Random, 95% CI)	1.44 [0.70, 2.99]

1.1 Homozygous Major	2	63	Risk Ratio (M‐H, Random, 95% CI)	1.62 [0.67, 3.96]
1.2 Heterozygous or Homozygous Minor	2	13	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.15, 5.70]

Comparison 20. Bupropion vs placebo ‐ rs1329650 ‐ non‐Hispanic black or African American

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Comparison 21. Bupropion vs placebo ‐ rs1028936 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	3	559	Risk Ratio (M‐H, Random, 95% CI)	1.39 [1.11, 1.74]

1.1 Homozygous Major	3	370	Risk Ratio (M‐H, Random, 95% CI)	1.54 [1.15, 2.06]
1.2 Heterozygous	3	175	Risk Ratio (M‐H, Random, 95% CI)	1.33 [0.75, 2.35]
1.3 Homozygous Minor	3	14	Risk Ratio (M‐H, Random, 95% CI)	1.60 [0.30, 8.49]

Comparison 21. Bupropion vs placebo ‐ rs1028936 ‐ non‐Hispanic white

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Comparison 22. Bupropion vs placebo ‐ rs1028936 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	76	Risk Ratio (M‐H, Random, 95% CI)	1.47 [0.68, 3.21]

1.1 Homozygous Major	2	65	Risk Ratio (M‐H, Random, 95% CI)	1.77 [0.74, 4.20]
1.2 Heterozygous or Homozygous Minor	2	11	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.09, 4.77]

Comparison 22. Bupropion vs placebo ‐ rs1028936 ‐ non‐Hispanic black or African American

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Comparison 23. Bupropion vs placebo ‐ rs215605 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	3	558	Risk Ratio (M‐H, Random, 95% CI)	1.48 [1.18, 1.87]

1.1 Homozygous Major	3	219	Risk Ratio (M‐H, Random, 95% CI)	1.77 [1.23, 2.55]
1.2 Heterozygous	3	259	Risk Ratio (M‐H, Random, 95% CI)	1.35 [0.98, 1.87]
1.3 Homozygous Minor	3	80	Risk Ratio (M‐H, Random, 95% CI)	1.12 [0.49, 2.55]

Comparison 23. Bupropion vs placebo ‐ rs215605 ‐ non‐Hispanic white

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Comparison 24. Bupropion vs placebo ‐ rs215605 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	76	Risk Ratio (M‐H, Random, 95% CI)	1.41 [0.54, 3.69]

1.1 Homozygous Major	2	49	Risk Ratio (M‐H, Random, 95% CI)	1.93 [0.15, 24.95]
1.2 Heterozygous or Homozygous Minor	2	27	Risk Ratio (M‐H, Random, 95% CI)	1.67 [0.46, 6.13]

Comparison 24. Bupropion vs placebo ‐ rs215605 ‐ non‐Hispanic black or African American

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Comparison 25. Bupropion + any NRT vs placebo ‐ rs1051730 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	444	Risk Ratio (M‐H, Random, 95% CI)	1.80 [1.07, 3.03]

1.1 Homozygous Major	2	183	Risk Ratio (M‐H, Random, 95% CI)	2.11 [0.31, 14.60]
1.2 Heterozygous	2	216	Risk Ratio (M‐H, Random, 95% CI)	1.82 [1.23, 2.69]
1.3 Homozygous Minor	2	45	Risk Ratio (M‐H, Random, 95% CI)	2.84 [0.90, 8.89]

Comparison 25. Bupropion + any NRT vs placebo ‐ rs1051730 ‐ non‐Hispanic white

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Comparison 26. Bupropion + any NRT vs placebo ‐ rs1051730 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	69	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.27, 3.07]

1.1 Homozygous Major	2	58	Risk Ratio (M‐H, Random, 95% CI)	1.64 [0.56, 4.83]
1.2 Heterozygous or Homozygous Minor	2	11	Risk Ratio (M‐H, Random, 95% CI)	0.22 [0.03, 1.43]

Comparison 26. Bupropion + any NRT vs placebo ‐ rs1051730 ‐ non‐Hispanic black or African American

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Comparison 27. Bupropion + any NRT vs placebo ‐ rs16969968 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	441	Risk Ratio (M‐H, Random, 95% CI)	1.79 [1.07, 2.99]

1.1 Homozygous Major	2	183	Risk Ratio (M‐H, Random, 95% CI)	2.11 [0.31, 14.60]
1.2 Heterozygous	2	215	Risk Ratio (M‐H, Random, 95% CI)	1.80 [1.22, 2.66]
1.3 Homozygous Minor	2	43	Risk Ratio (M‐H, Random, 95% CI)	2.81 [0.89, 8.88]

Comparison 27. Bupropion + any NRT vs placebo ‐ rs16969968 ‐ non‐Hispanic white

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Comparison 28. Bupropion + any NRT vs placebo ‐ rs16969968 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	69	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.46, 2.38]

1.1 Homozygous Major	2	63	Risk Ratio (M‐H, Random, 95% CI)	1.20 [0.51, 2.85]
1.2 Heterozygous or Homozygous Minor	2	6	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.03, 4.19]

Comparison 28. Bupropion + any NRT vs placebo ‐ rs16969968 ‐ non‐Hispanic black or African American

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Comparison 29. Bupropion + any NRT vs placebo ‐ rs2036527 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	443	Risk Ratio (M‐H, Random, 95% CI)	1.74 [1.09, 2.77]

1.1 Homozygous Major	2	181	Risk Ratio (M‐H, Random, 95% CI)	2.20 [0.33, 14.75]
1.2 Heterozygous	2	220	Risk Ratio (M‐H, Random, 95% CI)	1.83 [1.23, 2.72]
1.3 Homozygous Minor	2	42	Risk Ratio (M‐H, Random, 95% CI)	2.12 [0.79, 5.65]

Comparison 29. Bupropion + any NRT vs placebo ‐ rs2036527 ‐ non‐Hispanic white

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Comparison 30. Bupropion + any NRT vs placebo ‐ rs2036527 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	69	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.52, 1.92]

1.1 Homozygous Major	2	38	Risk Ratio (M‐H, Random, 95% CI)	2.03 [0.39, 10.56]
1.2 Heterozygous	2	23	Risk Ratio (M‐H, Random, 95% CI)	1.03 [0.38, 2.77]
1.3 Homozygous Minor	2	8	Risk Ratio (M‐H, Random, 95% CI)	0.74 [0.26, 2.05]

Comparison 30. Bupropion + any NRT vs placebo ‐ rs2036527 ‐ non‐Hispanic black or African American

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Comparison 31. Bupropion + any NRT vs placebo ‐ rs3733829 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	442	Risk Ratio (M‐H, Random, 95% CI)	1.55 [1.20, 2.01]

1.1 Homozygous Major	2	187	Risk Ratio (M‐H, Random, 95% CI)	1.48 [0.83, 2.65]
1.2 Heterozygous	2	201	Risk Ratio (M‐H, Random, 95% CI)	1.87 [1.04, 3.36]
1.3 Homozygous Minor	2	54	Risk Ratio (M‐H, Random, 95% CI)	1.85 [0.91, 3.74]

Comparison 31. Bupropion + any NRT vs placebo ‐ rs3733829 ‐ non‐Hispanic white

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Comparison 32. Bupropion + any NRT vs placebo ‐ rs3733829 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	48	Risk Ratio (M‐H, Random, 95% CI)	0.42 [0.14, 1.24]

1.1 Homozygous Major	2	48	Risk Ratio (M‐H, Random, 95% CI)	0.42 [0.14, 1.24]

Comparison 32. Bupropion + any NRT vs placebo ‐ rs3733829 ‐ non‐Hispanic black or African American

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Comparison 33. Bupropion + any NRT vs placebo ‐ rs7937 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	442	Risk Ratio (M‐H, Random, 95% CI)	1.51 [1.16, 1.97]

1.1 Homozygous Major	2	131	Risk Ratio (M‐H, Random, 95% CI)	2.00 [0.84, 4.75]
1.2 Heterozygous	2	229	Risk Ratio (M‐H, Random, 95% CI)	1.39 [0.99, 1.94]
1.3 Homozygous Minor	2	82	Risk Ratio (M‐H, Random, 95% CI)	2.34 [0.49, 11.08]

Comparison 33. Bupropion + any NRT vs placebo ‐ rs7937 ‐ non‐Hispanic white

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Comparison 34. Bupropion + any NRT vs placebo ‐ rs7937 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	69	Risk Ratio (M‐H, Random, 95% CI)	1.06 [0.47, 2.38]

1.1 Homozygous Major	2	31	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.40, 2.73]
1.2 Heterozygous or Homozygous Minor	2	38	Risk Ratio (M‐H, Random, 95% CI)	1.08 [0.23, 4.99]

Comparison 34. Bupropion + any NRT vs placebo ‐ rs7937 ‐ non‐Hispanic black or African American

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Comparison 35. Bupropion + any NRT vs placebo ‐ rs1329650 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	442	Risk Ratio (M‐H, Random, 95% CI)	1.62 [1.10, 2.39]

1.1 Homozygous Major	2	240	Risk Ratio (M‐H, Random, 95% CI)	1.98 [1.31, 3.00]
1.2 Heterozygous	2	172	Risk Ratio (M‐H, Random, 95% CI)	1.60 [0.70, 3.67]
1.3 Homozygous Minor	2	30	Risk Ratio (M‐H, Random, 95% CI)	2.04 [0.17, 25.25]

Comparison 35. Bupropion + any NRT vs placebo ‐ rs1329650 ‐ non‐Hispanic white

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Comparison 36. Bupropion + any NRT vs placebo ‐ rs1329650 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	69	Risk Ratio (M‐H, Random, 95% CI)	1.07 [0.48, 2.41]

1.1 Homozygous Major	2	55	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.40, 2.55]
1.2 Heterozygous or Homozygous Minor	2	14	Risk Ratio (M‐H, Random, 95% CI)	1.32 [0.26, 6.80]

Comparison 36. Bupropion + any NRT vs placebo ‐ rs1329650 ‐ non‐Hispanic black or African American

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Comparison 37. Bupropion + any NRT vs placebo ‐ rs1028936 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	444	Risk Ratio (M‐H, Random, 95% CI)	1.64 [1.08, 2.49]

1.1 Homozygous Major	2	305	Risk Ratio (M‐H, Random, 95% CI)	1.89 [1.34, 2.67]
1.2 Heterozygous	2	125	Risk Ratio (M‐H, Random, 95% CI)	1.42 [0.48, 4.20]
1.3 Homozygous Minor	2	14	Risk Ratio (M‐H, Random, 95% CI)	1.93 [0.47, 8.02]

Comparison 37. Bupropion + any NRT vs placebo ‐ rs1028936 ‐ non‐Hispanic white

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Comparison 38. Bupropion + any NRT vs placebo ‐ rs1028936 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	69	Risk Ratio (M‐H, Random, 95% CI)	1.07 [0.48, 2.41]

1.1 Homozygous Major	2	57	Risk Ratio (M‐H, Random, 95% CI)	1.10 [0.43, 2.84]
1.2 Heterozygous or Homozygous Minor	2	12	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.17, 5.39]

Comparison 38. Bupropion + any NRT vs placebo ‐ rs1028936 ‐ non‐Hispanic black or African American

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Comparison 39. Bupropion + any NRT vs placebo ‐ rs215605 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	442	Risk Ratio (M‐H, Random, 95% CI)	1.72 [1.16, 2.53]

1.1 Homozygous Major	2	171	Risk Ratio (M‐H, Random, 95% CI)	2.00 [1.32, 3.03]
1.2 Heterozygous	2	200	Risk Ratio (M‐H, Random, 95% CI)	1.47 [0.60, 3.63]
1.3 Homozygous Minor	2	71	Risk Ratio (M‐H, Random, 95% CI)	2.29 [0.72, 7.27]

Comparison 39. Bupropion + any NRT vs placebo ‐ rs215605 ‐ non‐Hispanic white

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Comparison 40. Bupropion + any NRT vs placebo ‐ rs215605 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	68	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.41, 1.77]

1.1 Homozygous Major	2	36	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.29, 1.76]
1.2 Heterozygous or Homozygous Minor	2	32	Risk Ratio (M‐H, Random, 95% CI)	1.19 [0.34, 4.13]

Comparison 40. Bupropion + any NRT vs placebo ‐ rs215605 ‐ non‐Hispanic black or African American

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Comparison 41. Bupropion + any NRT vs bupropion ‐ rs1051730 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	533	Risk Ratio (M‐H, Random, 95% CI)	1.18 [0.90, 1.55]

1.1 Homozygous Major	2	206	Risk Ratio (M‐H, Random, 95% CI)	1.14 [0.54, 2.42]
1.2 Heterozygous	2	262	Risk Ratio (M‐H, Random, 95% CI)	1.22 [0.93, 1.61]
1.3 Homozygous Minor	2	65	Risk Ratio (M‐H, Random, 95% CI)	1.28 [0.68, 2.44]

Comparison 41. Bupropion + any NRT vs bupropion ‐ rs1051730 ‐ non‐Hispanic white

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Comparison 42. Bupropion + any NRT vs bupropion ‐ rs1051730 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	87	Risk Ratio (M‐H, Random, 95% CI)	0.70 [0.37, 1.31]

1.1 Homozygous Major	2	66	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.40, 1.49]
1.2 Heterozygous or Homozygous Minor	2	21	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.05, 2.19]

Comparison 42. Bupropion + any NRT vs bupropion ‐ rs1051730 ‐ non‐Hispanic black or African American

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Comparison 43. Bupropion + any NRT vs bupropion ‐ rs16969968 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	531	Risk Ratio (M‐H, Random, 95% CI)	1.18 [0.90, 1.55]

1.1 Homozygous Major	2	206	Risk Ratio (M‐H, Random, 95% CI)	1.14 [0.54, 2.42]
1.2 Heterozygous	2	262	Risk Ratio (M‐H, Random, 95% CI)	1.22 [0.93, 1.61]
1.3 Homozygous Minor	2	63	Risk Ratio (M‐H, Random, 95% CI)	1.27 [0.66, 2.44]

Comparison 43. Bupropion + any NRT vs bupropion ‐ rs16969968 ‐ non‐Hispanic white

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Comparison 44. Bupropion + any NRT vs bupropion ‐ rs16969968 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	87	Risk Ratio (M‐H, Random, 95% CI)	0.69 [0.37, 1.27]

1.1 Homozygous Major	2	74	Risk Ratio (M‐H, Random, 95% CI)	0.73 [0.38, 1.40]
1.2 Heterozygous or Homozygous Minor	2	13	Risk Ratio (M‐H, Random, 95% CI)	0.41 [0.06, 2.76]

Comparison 44. Bupropion + any NRT vs bupropion ‐ rs16969968 ‐ non‐Hispanic black or African American

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Comparison 45. Bupropion + any NRT vs bupropion ‐ rs2036527 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	532	Risk Ratio (M‐H, Random, 95% CI)	1.18 [0.91, 1.52]

1.1 Homozygous Major	2	204	Risk Ratio (M‐H, Random, 95% CI)	1.17 [0.54, 2.52]
1.2 Heterozygous	2	264	Risk Ratio (M‐H, Random, 95% CI)	1.21 [0.92, 1.60]
1.3 Homozygous Minor	2	64	Risk Ratio (M‐H, Random, 95% CI)	1.24 [0.68, 2.25]

Comparison 45. Bupropion + any NRT vs bupropion ‐ rs2036527 ‐ non‐Hispanic white

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Comparison 46. Bupropion + any NRT vs bupropion ‐ rs2036527 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	87	Risk Ratio (M‐H, Random, 95% CI)	0.66 [0.35, 1.23]

1.1 Homozygous Major	2	50	Risk Ratio (M‐H, Random, 95% CI)	0.56 [0.23, 1.35]
1.2 Heterozygous or Homozygous Minor	2	37	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.32, 1.90]

Comparison 46. Bupropion + any NRT vs bupropion ‐ rs2036527 ‐ non‐Hispanic black or African American

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Comparison 47. Bupropion + any NRT vs bupropion ‐ rs3733829 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	531	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.96, 1.39]

1.1 Homozygous Major	2	236	Risk Ratio (M‐H, Random, 95% CI)	1.19 [0.77, 1.84]
1.2 Heterozygous	2	229	Risk Ratio (M‐H, Random, 95% CI)	1.11 [0.82, 1.51]
1.3 Homozygous Minor	2	66	Risk Ratio (M‐H, Random, 95% CI)	1.34 [0.80, 2.25]

Comparison 47. Bupropion + any NRT vs bupropion ‐ rs3733829 ‐ non‐Hispanic white

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Comparison 48. Bupropion + any NRT vs bupropion ‐ rs3733829 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	94	Risk Ratio (M‐H, Random, 95% CI)	0.49 [0.25, 0.99]

1.1 Homozygous Major	2	65	Risk Ratio (M‐H, Random, 95% CI)	0.43 [0.18, 1.01]
1.2 Heterozygous or Homozygous Minor	2	29	Risk Ratio (M‐H, Random, 95% CI)	0.73 [0.13, 4.20]

Comparison 48. Bupropion + any NRT vs bupropion ‐ rs3733829 ‐ non‐Hispanic black or African American

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Comparison 49. Bupropion + any NRT vs bupropion ‐ rs7937 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	533	Risk Ratio (M‐H, Random, 95% CI)	1.16 [0.95, 1.42]

1.1 Homozygous Major	2	145	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.65, 1.59]
1.2 Heterozygous	2	272	Risk Ratio (M‐H, Random, 95% CI)	1.27 [0.81, 2.00]
1.3 Homozygous Minor	2	116	Risk Ratio (M‐H, Random, 95% CI)	1.29 [0.90, 1.84]

Comparison 49. Bupropion + any NRT vs bupropion ‐ rs7937 ‐ non‐Hispanic white

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Comparison 50. Bupropion + any NRT vs bupropion ‐ rs7937 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	87	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.39, 1.43]

1.1 Homozygous Major	2	33	Risk Ratio (M‐H, Random, 95% CI)	0.61 [0.13, 2.86]
1.2 Heterozygous or Homozygous Minor	2	54	Risk Ratio (M‐H, Random, 95% CI)	0.73 [0.27, 1.93]

Comparison 50. Bupropion + any NRT vs bupropion ‐ rs7937 ‐ non‐Hispanic black or African American

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Comparison 51. Bupropion + any NRT vs bupropion ‐ rs1329650 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	531	Risk Ratio (M‐H, Random, 95% CI)	1.20 [0.97, 1.49]

1.1 Homozygous Major	2	279	Risk Ratio (M‐H, Random, 95% CI)	1.22 [0.66, 2.25]
1.2 Heterozygous	2	214	Risk Ratio (M‐H, Random, 95% CI)	1.22 [0.92, 1.62]
1.3 Homozygous Minor	2	38	Risk Ratio (M‐H, Random, 95% CI)	1.68 [0.89, 3.17]

Comparison 51. Bupropion + any NRT vs bupropion ‐ rs1329650 ‐ non‐Hispanic white

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Comparison 52. Bupropion + any NRT vs bupropion ‐ rs1329650 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	87	Risk Ratio (M‐H, Random, 95% CI)	0.63 [0.33, 1.20]

1.1 Homozygous Major	2	76	Risk Ratio (M‐H, Random, 95% CI)	0.59 [0.30, 1.15]
1.2 Heterozygous or Homozygous Minor	2	11	Risk Ratio (M‐H, Random, 95% CI)	1.2 [0.17, 8.24]

Comparison 52. Bupropion + any NRT vs bupropion ‐ rs1329650 ‐ non‐Hispanic black or African American

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Comparison 53. Bupropion + any NRT vs bupropion ‐ rs1028936 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	533	Risk Ratio (M‐H, Random, 95% CI)	1.18 [0.92, 1.50]

1.1 Homozygous Major	2	359	Risk Ratio (M‐H, Random, 95% CI)	1.09 [0.86, 1.37]
1.2 Heterozygous	2	159	Risk Ratio (M‐H, Random, 95% CI)	1.30 [0.62, 2.75]
1.3 Homozygous Minor	2	15	Risk Ratio (M‐H, Random, 95% CI)	2.17 [0.51, 9.18]

Comparison 53. Bupropion + any NRT vs bupropion ‐ rs1028936 ‐ non‐Hispanic white

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Comparison 54. Bupropion + any NRT vs bupropion ‐ rs1028936 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	87	Risk Ratio (M‐H, Random, 95% CI)	0.63 [0.33, 1.20]

1.1 Homozygous Major	2	76	Risk Ratio (M‐H, Random, 95% CI)	0.59 [0.30, 1.15]
1.2 Heterozygous or Homozygous Minor	2	11	Risk Ratio (M‐H, Random, 95% CI)	1.2 [0.17, 8.24]

Comparison 54. Bupropion + any NRT vs bupropion ‐ rs1028936 ‐ non‐Hispanic black or African American

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Comparison 55. Bupropion + any NRT vs bupropion ‐ rs215605 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	532	Risk Ratio (M‐H, Random, 95% CI)	1.17 [0.93, 1.47]

1.1 Homozygous Major	2	211	Risk Ratio (M‐H, Random, 95% CI)	1.28 [0.91, 1.80]
1.2 Heterozygous	2	241	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.69, 1.45]
1.3 Homozygous Minor	2	80	Risk Ratio (M‐H, Random, 95% CI)	1.61 [0.64, 4.08]

Comparison 55. Bupropion + any NRT vs bupropion ‐ rs215605 ‐ non‐Hispanic white

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Comparison 56. Bupropion + any NRT vs bupropion ‐ rs215605 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2	87	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.37, 1.35]

1.1 Homozygous Major	2	49	Risk Ratio (M‐H, Random, 95% CI)	0.51 [0.09, 2.94]
1.2 Heterozygous or Homozygous Minor	2	38	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.26, 1.93]

Comparison 56. Bupropion + any NRT vs bupropion ‐ rs215605 ‐ non‐Hispanic black or African American

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Comparison 57. Active NRT ‐ rs1051730 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	7		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	7	1559	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.71, 1.19]
1.2 Heterozygous vs Homozygous Minor	7	1650	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.75, 1.11]
2 End of Treatment Show forest plot	5		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Homozygous Minor	5	1200	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.73, 1.06]
2.2 Heterozygous vs Homozygous Minor	5	1291	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.79, 1.10]

Comparison 57. Active NRT ‐ rs1051730 ‐ non‐Hispanic white

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Comparison 58. Active NRT ‐ rs1051730 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	187	Risk Ratio (M‐H, Random, 95% CI)	1.08 [0.26, 4.57]
1.2 Heterozygous vs Homozygous Minor	2	56	Risk Ratio (M‐H, Random, 95% CI)	1.11 [0.25, 4.99]

Comparison 58. Active NRT ‐ rs1051730 ‐ non‐Hispanic black or African American

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Comparison 59. Active NRT ‐ rs16969968 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	392	Risk Ratio (M‐H, Random, 95% CI)	2.24 [0.92, 5.45]
2 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	392	Risk Ratio (M‐H, Random, 95% CI)	2.75 [1.08, 7.02]

Comparison 59. Active NRT ‐ rs16969968 ‐ non‐Hispanic black or African American

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Comparison 60. Active NRT ‐ rs588765 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	3	433	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.80, 1.37]
1.2 Heterozygous vs Homozygous Minor	3	546	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.76, 1.29]
2 End of Treatment Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Homozygous Minor	3	429	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.76, 1.18]
2.2 Heterozygous vs Homozygous Minor	3	542	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.77, 1.17]

Comparison 60. Active NRT ‐ rs588765 ‐ non‐Hispanic white

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Comparison 61. Active NRT ‐ rs2036527 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	501	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.60, 1.03]
1.2 Heterozygous vs Homozygous Minor	2	579	Risk Ratio (M‐H, Random, 95% CI)	0.83 [0.63, 1.10]
2 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Homozygous Minor	2	501	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.59, 1.35]
2.2 Heterozygous vs Homozygous Minor	2	579	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.61, 1.64]

Comparison 61. Active NRT ‐ rs2036527 ‐ non‐Hispanic white

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Comparison 62. Active NRT ‐ rs2036527 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	391	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.87, 1.81]
2 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	391	Risk Ratio (M‐H, Random, 95% CI)	1.73 [1.20, 2.49]

Comparison 62. Active NRT ‐ rs2036527 ‐ non‐Hispanic black or African American

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Comparison 63. Active NRT ‐ DRD‐4 (exon 3 48 bp) ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	3	866	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.51, 1.76]
1.2 Heterozygous vs Homozygous Minor	3	321	Risk Ratio (M‐H, Random, 95% CI)	0.81 [0.42, 1.60]
2 End of Treatment Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Homozygous Minor	3	866	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.71, 1.23]
2.2 Heterozygous vs Homozygous Minor	3	321	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.58, 1.26]

Comparison 63. Active NRT ‐ DRD‐4 (exon 3 48 bp) ‐ non‐Hispanic white

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Comparison 64. Active NRT ‐ SLC6A4 (Promoter) ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	461	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.50, 1.67]
1.2 Heterozygous vs Homozygous Minor	2	649	Risk Ratio (M‐H, Random, 95% CI)	1.12 [0.66, 1.90]
2 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Homozygous Minor	2	461	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.77, 1.23]
2.2 Heterozygous vs Homozygous Minor	2	649	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.74, 1.18]

Comparison 64. Active NRT ‐ SLC6A4 (Promoter) ‐ non‐Hispanic white

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Comparison 65. Active NRT‐NMR ‐ non‐Hispanic white or black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Normal NMR vs Slow NMR	2	718	Risk Ratio (M‐H, Random, 95% CI)	0.54 [0.37, 0.78]
2 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Normal NMR vs Slow NMR	2	718	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.58, 1.03]

Comparison 65. Active NRT‐NMR ‐ non‐Hispanic white or black or African American

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Comparison 66. Bupropion ‐ rs1051730 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	4	316	Risk Ratio (M‐H, Random, 95% CI)	1.27 [0.67, 2.43]
1.2 Heterozygous vs Homozygous Minor	4	390	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.65, 2.03]
2 End of Treatment Show forest plot	6		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Homozygous Minor	6	386	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.88, 1.50]
2.2 Heterozygous vs Homozygous Minor	6	480	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.81, 1.33]

Comparison 66. Bupropion ‐ rs1051730 ‐ non‐Hispanic white

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Comparison 67. Bupropion ‐ rs1051730 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	63	Risk Ratio (M‐H, Random, 95% CI)	0.83 [0.36, 1.95]
2 End of Treatment Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Heterozygous or Homozygous Minor	3	84	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.51, 1.72]

Comparison 67. Bupropion ‐ rs1051730 ‐ non‐Hispanic black or African American

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Comparison 68. Bupropion ‐ rs16969968 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	3	160	Risk Ratio (M‐H, Random, 95% CI)	1.47 [0.96, 2.25]
1.2 Heterozygous vs Homozygous Minor	3	216	Risk Ratio (M‐H, Random, 95% CI)	1.20 [0.79, 1.84]

Comparison 68. Bupropion ‐ rs16969968 ‐ non‐Hispanic white

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Comparison 69. Bupropion ‐ rs16969968 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	294	Risk Ratio (M‐H, Random, 95% CI)	0.62 [0.31, 1.21]
2 End of Treatment Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Heterozygous or Homozygous Minor	3	315	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.48, 1.32]

Comparison 69. Bupropion ‐ rs16969968 ‐ non‐Hispanic black or African American

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Comparison 70. Bupropion ‐ rs588765 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	4	304	Risk Ratio (M‐H, Random, 95% CI)	0.83 [0.52, 1.34]
1.2 Heterozygous vs Homozygous Minor	4	401	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.66, 1.21]
2 End of Treatment Show forest plot	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Homozygous Minor	4	304	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.69, 1.14]
2.2 Heterozygous vs Homozygous Minor	4	400	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.76, 1.22]

Comparison 70. Bupropion ‐ rs588765 ‐ non‐Hispanic white

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Comparison 71. Bupropion ‐ rs2036527 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	208	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.33, 1.81]
1.2 Heterozygous vs Homozygous Minor	2	269	Risk Ratio (M‐H, Random, 95% CI)	0.83 [0.51, 1.37]
2 End of Treatment Show forest plot	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Homozygous Minor	4	277	Risk Ratio (M‐H, Random, 95% CI)	1.16 [0.79, 1.70]
2.2 Heterozygous vs Homozygous Minor	4	361	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.61, 1.51]

Comparison 71. Bupropion ‐ rs2036527 ‐ non‐Hispanic white

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Comparison 72. Bupropion ‐ rs2036527 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	3	331	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.55, 1.46]
2 End of Treatment Show forest plot	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Heterozygous or Homozygous Minor	4	352	Risk Ratio (M‐H, Random, 95% CI)	1.24 [0.87, 1.76]

Comparison 72. Bupropion ‐ rs2036527 ‐ non‐Hispanic black or African American

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Comparison 73. Bupropion ‐ rs3733829 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	191	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.56, 1.46]
1.2 Heterozygous vs Homozygous Minor	2	161	Risk Ratio (M‐H, Random, 95% CI)	1.06 [0.65, 1.71]
2 End of Treatment Show forest plot	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Homozygous Minor	4	259	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.73, 1.40]
2.2 Heterozygous vs Homozygous Minor	4	237	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.70, 1.36]

Comparison 73. Bupropion ‐ rs3733829 ‐ non‐Hispanic white

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Comparison 74. Bupropion ‐ rs3733829 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	46	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.37, 2.99]

Comparison 74. Bupropion ‐ rs3733829 ‐ non‐Hispanic black or African American

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Comparison 75. Bupropion ‐ rs7937 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	3	159	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.71, 1.40]
1.2 Heterozygous vs Homozygous Minor	3	238	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.65, 1.23]

Comparison 75. Bupropion ‐ rs7937 ‐ non‐Hispanic white

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Comparison 76. Bupropion ‐ rs7937 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	23	Risk Ratio (M‐H, Random, 95% CI)	1.16 [0.32, 4.26]
1.2 Heterozygous vs Homozygous Minor	2	27	Risk Ratio (M‐H, Random, 95% CI)	0.72 [0.18, 2.93]

Comparison 76. Bupropion ‐ rs7937 ‐ non‐Hispanic black or African American

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Comparison 77. Bupropion ‐ rs1329650 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	3	186	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.54, 1.35]
1.2 Heterozygous vs Homozygous Minor	3	163	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.56, 1.42]

Comparison 77. Bupropion ‐ rs1329650 ‐ non‐Hispanic white

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Comparison 78. Bupropion ‐ rs1329650 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	47	Risk Ratio (M‐H, Random, 95% CI)	1.46 [0.35, 6.01]

Comparison 78. Bupropion ‐ rs1329650 ‐ non‐Hispanic black or African American

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Comparison 79. Bupropion ‐ rs1028936 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	3	221	Risk Ratio (M‐H, Random, 95% CI)	0.81 [0.42, 1.55]
1.2 Heterozygous vs Homozygous Minor	3	112	Risk Ratio (M‐H, Random, 95% CI)	0.81 [0.40, 1.64]

Comparison 79. Bupropion ‐ rs1028936 ‐ non‐Hispanic white

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Comparison 80. Bupropion ‐ rs1028936 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	47	Risk Ratio (M‐H, Random, 95% CI)	1.46 [0.35, 6.01]

Comparison 80. Bupropion ‐ rs1028936 ‐ non‐Hispanic black or African American

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Comparison 81. Bupropion ‐ rs215605 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	3	170	Risk Ratio (M‐H, Random, 95% CI)	1.61 [0.87, 3.00]
1.2 Heterozygous vs Homozygous Minor	3	199	Risk Ratio (M‐H, Random, 95% CI)	1.56 [0.79, 3.06]

Comparison 81. Bupropion ‐ rs215605 ‐ non‐Hispanic white

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Comparison 82. Bupropion ‐ rs215605 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	47	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.54, 2.44]

Comparison 82. Bupropion ‐ rs215605 ‐ non‐Hispanic black or African American

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Comparison 83. Varenicline ‐ rs16969968 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	358	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.71, 1.25]
1.2 Heterozygous vs Homozygous Minor	2	438	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.75, 1.30]
2 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Homozygous Minor	2	358	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.78, 1.24]
2.2 Heterozygous vs Homozygous Minor	2	438	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.77, 1.22]

Comparison 83. Varenicline ‐ rs16969968 ‐ non‐Hispanic white

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Comparison 84. Varenicline ‐ rs588765 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	354	Risk Ratio (M‐H, Random, 95% CI)	1.20 [0.91, 1.60]
1.2 Heterozygous vs Homozygous Minor	2	465	Risk Ratio (M‐H, Random, 95% CI)	1.18 [0.90, 1.54]
2 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Homozygous Minor	2	354	Risk Ratio (M‐H, Random, 95% CI)	1.14 [0.91, 1.43]
2.2 Heterozygous vs Homozygous Minor	2	465	Risk Ratio (M‐H, Random, 95% CI)	1.10 [0.89, 1.37]

Comparison 84. Varenicline ‐ rs588765 ‐ non‐Hispanic white

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Comparison 85. Bupropion + any NRT ‐ rs1051730 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	138	Risk Ratio (M‐H, Random, 95% CI)	1.10 [0.67, 1.78]
1.2 Heterozygous vs Homozygous Minor	2	155	Risk Ratio (M‐H, Random, 95% CI)	1.11 [0.69, 1.80]

Comparison 85. Bupropion + any NRT ‐ rs1051730 ‐ non‐Hispanic white

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Comparison 86. Bupropion + any NRT ‐ rs1051730 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	40	Risk Ratio (M‐H, Random, 95% CI)	2.26 [0.36, 14.38]

Comparison 86. Bupropion + any NRT ‐ rs1051730 ‐ non‐Hispanic black or African American

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Comparison 87. Bupropion + any NRT ‐ rs16969968 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	136	Risk Ratio (M‐H, Random, 95% CI)	1.12 [0.67, 1.85]
1.2 Heterozygous vs Homozygous Minor	2	153	Risk Ratio (M‐H, Random, 95% CI)	1.13 [0.68, 1.86]

Comparison 87. Bupropion + any NRT ‐ rs16969968 ‐ non‐Hispanic white

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Comparison 88. Bupropion + any NRT ‐ rs16969968 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	40	Risk Ratio (M‐H, Random, 95% CI)	1.66 [0.27, 10.32]

Comparison 88. Bupropion + any NRT ‐ rs16969968 ‐ non‐Hispanic black or African American

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Comparison 89. Bupropion + any NRT ‐ rs2036527 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	135	Risk Ratio (M‐H, Random, 95% CI)	1.12 [0.70, 1.79]
1.2 Heterozygous vs Homozygous Minor	2	156	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.65, 1.66]

Comparison 89. Bupropion + any NRT ‐ rs2036527 ‐ non‐Hispanic white

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Comparison 90. Bupropion + any NRT ‐ rs2036527 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	28	Risk Ratio (M‐H, Random, 95% CI)	0.51 [0.06, 4.51]
1.2 Heterozygous vs Homozygous Minor	2	17	Risk Ratio (M‐H, Random, 95% CI)	0.70 [0.03, 15.98]

Comparison 90. Bupropion + any NRT ‐ rs2036527 ‐ non‐Hispanic black or African American

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Comparison 91. Bupropion + any NRT ‐ rs3733829 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	144	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.66, 1.34]
1.2 Heterozygous vs Homozygous Minor	2	153	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.55, 1.14]

Comparison 91. Bupropion + any NRT ‐ rs3733829 ‐ non‐Hispanic white

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Comparison 92. Bupropion + any NRT ‐ rs3733829 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	40	Risk Ratio (M‐H, Random, 95% CI)	0.36 [0.13, 0.99]

Comparison 92. Bupropion + any NRT ‐ rs3733829 ‐ non‐Hispanic black or African American

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Comparison 93. Bupropion + any NRT ‐ rs7937 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	128	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.57, 1.10]
1.2 Heterozygous vs Homozygous Minor	2	194	Risk Ratio (M‐H, Random, 95% CI)	0.81 [0.51, 1.28]

Comparison 93. Bupropion + any NRT ‐ rs7937 ‐ non‐Hispanic white

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Comparison 94. Bupropion + any NRT ‐ rs7937 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	40	Risk Ratio (M‐H, Random, 95% CI)	1.29 [0.12, 13.56]

Comparison 94. Bupropion + any NRT ‐ rs7937 ‐ non‐Hispanic black or African American

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Comparison 95. Bupropion + any NRT ‐ rs1329650 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	170	Risk Ratio (M‐H, Random, 95% CI)	0.64 [0.43, 0.94]
1.2 Heterozygous vs Homozygous Minor	2	117	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.50, 1.03]

Comparison 95. Bupropion + any NRT ‐ rs1329650 ‐ non‐Hispanic white

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Comparison 96. Bupropion + any NRT ‐ rs1329650 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	40	Risk Ratio (M‐H, Random, 95% CI)	0.54 [0.15, 1.94]

Comparison 96. Bupropion + any NRT ‐ rs1329650 ‐ non‐Hispanic black or African American

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Comparison 97. Bupropion + any NRT ‐ rs1028936 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	193	Risk Ratio (M‐H, Random, 95% CI)	0.63 [0.37, 1.07]
1.2 Heterozygous vs Homozygous Minor	2	85	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.42, 1.32]

Comparison 97. Bupropion + any NRT ‐ rs1028936 ‐ non‐Hispanic white

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Comparison 98. Bupropion + any NRT ‐ rs1028936 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	40	Risk Ratio (M‐H, Random, 95% CI)	0.54 [0.15, 1.94]

Comparison 98. Bupropion + any NRT ‐ rs1028936 ‐ non‐Hispanic black or African American

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Comparison 99. Bupropion + any NRT ‐ rs215605 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	148	Risk Ratio (M‐H, Random, 95% CI)	1.18 [0.84, 1.66]
1.2 Heterozygous vs Homozygous Minor	2	162	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.61, 1.26]

Comparison 99. Bupropion + any NRT ‐ rs215605 ‐ non‐Hispanic white

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Comparison 100. Bupropion + any NRT ‐ rs215605 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	40	Risk Ratio (M‐H, Random, 95% CI)	0.76 [0.04, 13.56]

Comparison 100. Bupropion + any NRT ‐ rs215605 ‐ non‐Hispanic black or African American

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Comparison 101. Placebo ‐ rs1051730 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	6		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	6	533	Risk Ratio (M‐H, Random, 95% CI)	1.29 [0.86, 1.92]
1.2 Heterozygous vs Homozygous Minor	6	597	Risk Ratio (M‐H, Random, 95% CI)	1.08 [0.72, 1.62]
2 End of Treatment Show forest plot	7		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Homozygous Minor	7	542	Risk Ratio (M‐H, Random, 95% CI)	1.39 [0.91, 2.13]
2.2 Heterozygous vs Homozygous Minor	7	605	Risk Ratio (M‐H, Random, 95% CI)	1.24 [0.81, 1.89]

Comparison 101. Placebo ‐ rs1051730 ‐ non‐Hispanic white

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Comparison 102. Placebo ‐ rs1051730 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	63	Risk Ratio (M‐H, Random, 95% CI)	0.73 [0.08, 6.73]
2 End of Treatment Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Heterozygous or Homozygous Minor	3	83	Risk Ratio (M‐H, Random, 95% CI)	0.76 [0.24, 2.45]

Comparison 102. Placebo ‐ rs1051730 ‐ non‐Hispanic black or African American

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Comparison 103. Placebo ‐ rs16969968 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	162	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.51, 2.14]
1.2 Heterozygous vs Homozygous Minor	2	211	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.32, 1.96]
2 End of Treatment Show forest plot	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Homozygous Minor	4	218	Risk Ratio (M‐H, Random, 95% CI)	1.55 [0.68, 3.53]
2.2 Heterozygous vs Homozygous Minor	4	276	Risk Ratio (M‐H, Random, 95% CI)	1.34 [0.51, 3.53]

Comparison 103. Placebo ‐ rs16969968 ‐ non‐Hispanic white

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Comparison 104. Placebo ‐ rs16969968 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	3	584	Risk Ratio (M‐H, Random, 95% CI)	0.74 [0.42, 1.33]
2 End of Treatment Show forest plot	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Heterozygous or Homozygous Minor	4	596	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.35, 0.86]

Comparison 104. Placebo ‐ rs16969968 ‐ non‐Hispanic black or African American

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Comparison 105. Placebo ‐ rs588765 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	5		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	5	383	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.69, 1.57]
1.2 Heterozygous vs Homozygous Minor	5	470	Risk Ratio (M‐H, Random, 95% CI)	1.07 [0.72, 1.58]
2 End of Treatment Show forest plot	5		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Homozygous Minor	5	362	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.63, 1.21]
2.2 Heterozygous vs Homozygous Minor	5	404	Risk Ratio (M‐H, Random, 95% CI)	1.08 [0.80, 1.46]

Comparison 105. Placebo ‐ rs588765 ‐ non‐Hispanic white

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Comparison 106. Placebo ‐ rs588765 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	566	Risk Ratio (M‐H, Random, 95% CI)	1.20 [0.80, 1.79]
2 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	566	Risk Ratio (M‐H, Random, 95% CI)	1.12 [0.71, 1.77]

Comparison 106. Placebo ‐ rs588765 ‐ non‐Hispanic black or African American

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Comparison 107. Placebo ‐ rs2036527 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	160	Risk Ratio (M‐H, Random, 95% CI)	1.85 [0.77, 4.44]
1.2 Heterozygous vs Homozygous Minor	2	209	Risk Ratio (M‐H, Random, 95% CI)	1.58 [0.66, 3.77]
2 End of Treatment Show forest plot	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Homozygous Minor	4	216	Risk Ratio (M‐H, Random, 95% CI)	1.98 [0.91, 4.35]
2.2 Heterozygous vs Homozygous Minor	4	275	Risk Ratio (M‐H, Random, 95% CI)	1.86 [0.94, 3.69]

Comparison 107. Placebo ‐ rs2036527 ‐ non‐Hispanic white

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Comparison 108. Placebo ‐ rs2036527 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	4	629	Risk Ratio (M‐H, Random, 95% CI)	1.12 [0.71, 1.77]
2 End of Treatment Show forest plot	5		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Heterozygous or Homozygous Minor	5	641	Risk Ratio (M‐H, Random, 95% CI)	1.08 [0.71, 1.64]

Comparison 108. Placebo ‐ rs2036527 ‐ non‐Hispanic black or African American

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Comparison 109. Placebo ‐ DRD‐4 (exon 3 48 bp) ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	3	387	Risk Ratio (M‐H, Random, 95% CI)	1.07 [0.37, 3.16]
1.2 Heterozygous vs Homozygous Minor	3	212	Risk Ratio (M‐H, Random, 95% CI)	0.60 [0.22, 1.63]
2 End of Treatment Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Homozygous Minor	3	387	Risk Ratio (M‐H, Random, 95% CI)	1.08 [0.51, 2.29]
2.2 Heterozygous vs Homozygous Minor	3	212	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.61, 1.29]

Comparison 109. Placebo ‐ DRD‐4 (exon 3 48 bp) ‐ non‐Hispanic white

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Comparison 110. Placebo ‐ rs3733829 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	2	162	Risk Ratio (M‐H, Random, 95% CI)	0.84 [0.46, 1.51]
1.2 Heterozygous vs Homozygous Minor	2	142	Risk Ratio (M‐H, Random, 95% CI)	0.66 [0.35, 1.26]
2 End of Treatment Show forest plot	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major vs Homozygous Minor	4	215	Risk Ratio (M‐H, Random, 95% CI)	1.23 [0.74, 2.05]
2.2 Heterozygous vs Homozygous Minor	4	203	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.57, 1.65]

Comparison 110. Placebo ‐ rs3733829 ‐ non‐Hispanic white

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Comparison 111. Placebo ‐ rs7937 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	3	113	Risk Ratio (M‐H, Random, 95% CI)	0.81 [0.45, 1.45]
1.2 Heterozygous vs Homozygous Minor	3	160	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.57, 1.60]

Comparison 111. Placebo ‐ rs7937 ‐ non‐Hispanic white

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Comparison 112. Placebo ‐ rs7937 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	29	Risk Ratio (M‐H, Random, 95% CI)	1.17 [0.27, 5.04]

Comparison 112. Placebo ‐ rs7937 ‐ non‐Hispanic black or African American

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Comparison 113. Placebo ‐ rs1329650 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	3	129	Risk Ratio (M‐H, Random, 95% CI)	0.81 [0.18, 3.62]
1.2 Heterozygous vs Homozygous Minor	3	116	Risk Ratio (M‐H, Random, 95% CI)	0.80 [0.39, 1.63]

Comparison 113. Placebo ‐ rs1329650 ‐ non‐Hispanic white

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Comparison 114. Placebo ‐ rs1329650 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	29	Risk Ratio (M‐H, Random, 95% CI)	0.72 [0.19, 2.78]

Comparison 114. Placebo ‐ rs1329650 ‐ non‐Hispanic black or African American

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Comparison 115. Placebo ‐ rs1028936 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	3	163	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.29, 3.14]
1.2 Heterozygous vs Homozygous Minor	3	77	Risk Ratio (M‐H, Random, 95% CI)	1.20 [0.36, 4.03]

Comparison 115. Placebo ‐ rs1028936 ‐ non‐Hispanic white

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Comparison 116. Placebo ‐ rs1028936 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	29	Risk Ratio (M‐H, Random, 95% CI)	0.49 [0.18, 1.32]

Comparison 116. Placebo ‐ rs1028936 ‐ non‐Hispanic black or African American

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Comparison 117. Placebo ‐ rs215605 ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Homozygous Minor	3	129	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.52, 1.82]
1.2 Heterozygous vs Homozygous Minor	3	140	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.63, 2.12]

Comparison 117. Placebo ‐ rs215605 ‐ non‐Hispanic white

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Comparison 118. Placebo ‐ rs215605 ‐ non‐Hispanic black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major vs Heterozygous or Homozygous Minor	2	29	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.03, 38.58]

Comparison 118. Placebo ‐ rs215605 ‐ non‐Hispanic black or African American

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Comparison 119. Placebo ‐ SLC6A4 (Promoter) ‐ non‐Hispanic white

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Homozygous Major or Heterozygous vs Homozygous Minor	2	151	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.32, 1.79]
2 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Homozygous Major or Heterozygous vs Homozygous Minor	2	151	Risk Ratio (M‐H, Random, 95% CI)	1.07 [0.83, 1.38]

Comparison 119. Placebo ‐ SLC6A4 (Promoter) ‐ non‐Hispanic white

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Comparison 120. Placebo ‐ NMR ‐ non‐Hispanic white or black or African American

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Six‐Month Abstinence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Normal NMR vs Slow NMR	2	699	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.70, 1.48]
2 End of Treatment Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Normal NMR vs Slow NMR	2	718	Risk Ratio (M‐H, Random, 95% CI)	0.63 [0.35, 1.14]

Comparison 120. Placebo ‐ NMR ‐ non‐Hispanic white or black or African American

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