Table 4.
Gender stratified SNP × treatment interaction results at 6-month follow-up
| SNP | Gene Region | Gender | MAF | Placebo | Bupropion | Patch | Spray | Test of Interactiona | |
|---|---|---|---|---|---|---|---|---|---|
| SNP OR (95% CI) | SNP OR (95% CI) | SNP OR (95% CI) | SNP OR (95% CI) | Observed P | Adjusted P | ||||
| Significant SNPs within Males | |||||||||
| rs806365b | CNR1 | Male | 0.46 | 1.06 (0.30–3.75) | 2.05 (0.62–6.78) | 2.41 (0.74–7.84) | 0.04 (0.01–0.21) | 3.76 × 10−6 | 3.86 × 10−5 |
| Female | 0.44 | 0.30 (0.11–0.87) | 0.80 (0.33–1.92) | 0.53 (0.14–1.95) | 1.32 (0.43–4.12) | 2.66 × 10−1 | 7.34 × 10−1 | ||
|
| |||||||||
| rs684513 | CHRNA5 | Male | 0.17 | 1.56 (0.51–4.74) | 0.57 (0.19–1.74) | 4.00 (1.53–10.42) | 0.11 (0.02–0.50) | 7.74 × 10−5 | 6.98 × 10−4 |
| Female | 0.15 | 1.56 (0.51–4.72) | 1.84 (0.71–4.73) | 1.19 (0.31–4.50) | 1.59 (0.55–4.59) | 9.64 × 10−1 | 9.64 × 10−1 | ||
|
| |||||||||
| rs4887069 | CHRNA3:CHRNB4 | Male | 0.2 | 1.83 (0.72–4.61) | 0.62 (0.22–1.72) | 2.63 (1.24–5.55) ) | 0.17 (0.04–0.61) | 2.83 × 10−4 | 2.30 × 10−3 |
| Female | 0.17 | 1.22 (0.46–3.27) | 0.91 (0.39–2.15) | 1.51 (0.46–5.01 | 0.69 (0.29–1.66) | 7.19 × 10−1 | 9.73 × 10−1 | ||
|
| |||||||||
| rs938682 | CHRNA3 | Male | 0.2 | 2.10 (0.79–5.57) | 0.62 (0.23–1.72) | 2.24 (1.07–4.67) | 0.17 (0.04–0.61) | 5.43 × 10−4 | 4.20 × 10−3 |
| Female | 0.16 | 1.26 (0.47–3.36) | 1.33 (0.58–3.06) | 1.08 (0.31–3.79) | 0.75 (0.32–1.78) | 7.88 × 101 | 9.48 × 10−1 | ||
|
| |||||||||
| rs637137 | CHRNA5 | Male | 0.2 | 1.85 (0.70–4.93) | 0.67 (0.24–1.86) | 2.38 (1.14–4.97) | 0.17 (0.04–0.61) | 6.30 × 10−4 | 4.81 × 10−3 |
| Female | 0.16 | 1.54 (0.60–3.98) | 1.33 (0.58–3.06) | 1.17 (0.31–4.43) | 0.73 (0.32–1.71) | 6.51 × 10−1 | 9.76 × 10−1 | ||
|
| |||||||||
| rs3743078 | CHRNA3;CHRNA5 | Male | 0.21 | 1.97 (0.81–4.81) | 0.71 (0.27–1.87) | 2.24 (1.07–4.67) | 0.17 (0.04–0.61) | 6.79 × 10−4 | 5.13 × 10−3 |
| Female | 0.16 | 1.13 (0.42–3.03) | 1.33 (0.58–3.06) | 1.17 (0.31–4.43) | 0.75 (0.32–1.78) | 8.07 × 10−1 | 9.59 × 10−1 | ||
|
| |||||||||
| rs667282 | CHRNA5 | Male | 0.2 | 1.85 (0.69–4.92) | 0.67 (0.24–1.86) | 2.32 (1.11–4.86) | 0.17 (0.04–0.61) | 7.10 × 10−4 | 5.30 × 10−3 |
| Female | 0.16 | 1.54 (0.60–3.98) | 1.33 (0.58–3.06) | 1.17 (0.31–4.43) | 0.73 (0.32–1.71) | 6.51 × 10−1 | 9.76 × 10−1 | ||
|
| |||||||||
| rs11954565 | DRD1 | Male | 0.34 | 2.77 (0.81–9.47) | 1.43 (0.57–3.59) | 0.59 (0.23–1.48) | 0.09 (0.02–0.43) | 5.83 × 10−4 | 6.66 × 10−3 |
| Female | 0.36 | 3.12 (0.84–11.64) | 1.76 (0.73–4.23) | 1.20 (0.32–4.54) | 1.11 (0.41–3.01) | 6.08 × 10−1 | 9.42 × 10−1 | ||
|
| |||||||||
| rs806369b | CNR1 | Male | 0.31 | 2.16 (0.97–4.79) | 1.31 (0.64–2.71) | 1.68 (0.82–3.42) | 0.14 (0.03–0.63) | 7.65 × 10−4 | 6.80 × 10−3 |
| Female | 0.3 | 0.55 (0.23–1.32) | 0.80 (0.43–1.49) | 0.45 (0.13–1.52) | 1.42 (0.63–3.22) | 3.14 × 10−1 | 7.88 × 10−1 | ||
|
| |||||||||
| rs6495309 | CHRNA3;CHRNB4 | Male | 0.19 | 2.19 (0.83–5.81) | 0.67 (0.24–1.86) | 1.98 (0.87–4.53) | 0.17 (0.05–0.61) | 1.37 × 10−3 | 9.26 × 10−3 |
| Female | 0.15 | 1.45 (0.54–3.86) | 0.96 (0.40–2.31) | 0.81 (0.21–3.16) | 0.80 (0.33–1.92) | 8.33 × 10−1 | 9.55 × 10−1 | ||
|
| |||||||||
| rs934778 | POMC | Male | 0.32 | 1.73 (0.54–5.53) | 2.35 (0.92–5.99) | 0.21 (0.07–0.61) | 0.85 (0.30–2.42) | 2.85 × 10−3 | 1.51 × 10−2 |
| Female | 0.34 | 0.94 (0.34–2.60) | 3.11 (1.20–8.01) | 2.45 (0.60–10.09) | 0.84 (0.31–2.29) | 1.75 × 10−1 | 4.35 × 10−1 | ||
|
| |||||||||
| rs708905b | FOSB | Male | 0.14 | 0.14 (0.02–1.17) | 2.52 (0.91–7.02) | 0.27 (0.07–0.98) | 1.29 (0.42–3.93) | 5.68 × 10−3 | 2.54 × 10−2 |
| Female | 0.13 | 0.72 (0.21–2.40) | 0.72 (0.24–2.15) | 3.14 (0.74–13.29) | 0.37 (0.10–1.39) | 1.91 × 10−1 | 4.04 × 10−1 | ||
|
| |||||||||
| rs743409b | MAPK1 | Male | 0.44 | 0.37 (0.15–0.94) | 1.22 (0.64–2.35) | 0.97 (0.52–1.80) | 2.95 (1.33–6.54) | 5.47 × 10−3 | 2.55 × 10−2 |
| Female | 0.47 | 2.10 (1.02–4.33) | 0.81 (0.46–1.42) | 1.57 (0.63–3.96) | 1.05 (0.55–2.00) | 1.84 × 10−1 | 4.72 × 10−1 | ||
|
| |||||||||
| rs2267366 | PRKCABP | Male | 0.13 | 0.61 (0.16–2.28) | 0.53 (0.20–1.41) | 0.73 (0.25–2.12) | 5.32 (1.80–15.74) | 6.33 × 10−3 | 2.64 × 10−2 |
| Female | 0.16 | 0.86 (0.33–2.29) | 0.76 (0.34–1.70) | 0.47 (0.07–3.33) | 0.56 (0.19–1.63) | 9.03 × 10−1 | 9.03 × 10−1 | ||
|
| |||||||||
| rs1892848b | MAPK1 | Male | 0.45 | 0.35 (0.14–0.90) | 1.14 (0.60–2.18) | 0.97 (0.52–1.81) | 2.79 (1.23–6.33) | 7.26 × 10−3 | 3.24 × 10−2 |
| Female | 0.47 | 2.29 (1.09–4.80) | 0.79 (0.45–1.40) | 1.57 (0.63–3.96) | 1.05 (0.55–2.00) | 1.27 × 10−1 | 3.52 × 10−1 | ||
|
| |||||||||
| rs3788332b | MAPK1 | Male | 0.45 | 0.35 (0.14–0.90) | 1.14 (0.60–2.18) | 0.97 (0.52–1.81) | 2.79 (1.23–6.33) | 7.26 × 10−3 | 3.25 × 10−2 |
| Female | 0.47 | 2.38 (1.12–5.02) | 0.77 (0.43–1.37) | 1.57 (0.63–3.92) | 1.05 (0.55–2.00) | 9.92 × 10−2 | 2.88 × 10−1 | ||
|
| |||||||||
| rs5999550b | MAPK1 | Male | 0.45 | 0.35 (0.14–0.90) | 1.14 (0.60–2.18) | 0.97 (0.52–1.81) | 2.79 (1.23–6.33) | 7.26 × 10−3 | 3.25 × 10−2 |
| Female | 0.47 | 2.29 (1.09–4.80) | 0.79 (0.45–1.40) | 1.57 (0.63–3.96) | 1.05 (0.55–2.00) | 1.27 × 10−1 | 3.52 × 10−1 | ||
|
| |||||||||
| rs11704205b | MAPK1 | Male | 0.45 | 0.35 (0.14–0.90) | 1.14 (0.60–2.18) | 0.97 (0.52–1.81) | 2.79 (1.23–6.33) | 7.26 × 10−3 | 3.26 × 10−2 |
| Female | 0.47 | 2.29 (1.09–4.80) | 0.79 (0.45–1.40) | 1.57 (0.63–3.96) | 1.05 (0.55–2.00) | 1.27 × 10−1 | 3.52 × 10−1 | ||
|
| |||||||||
| rs2797855 | DBH | Male | 0.4 | 1.91 (0.56–6.57) | 0.17 (0.06–0.45) | 0.41 (0.16–1.02) | 1.32 (0.45–3.81) | 4.14 × 10−3 | 4.74 × 10−2 |
| Female | 0.45 | 0.91 (0.29–2.84) | 1.39 (0.57–3.40) | 0.77 (0.20–2.94) | 0.31 (0.11–0.87) | 1.86 × 10−1 | 7.44 × 10−1 | ||
|
| |||||||||
| Significant SNPs within Females | |||||||||
| rs10423854b | FOSB | Male | 0.43 | 1.12 (0.35–3.61) | 1.05 (0.41–2.72) | 0.38 (0.15–0.96) | 1.78 (0.57–5.54) | 1.69 × 10−1 | 4.26 × 10−1 |
| Female | 0.41 | 0.19 (0.06–0.55) | 0.48 (0.20–1.14) | 6.33 (0.76–52.37) | 1.14 (0.40–3.19) | 2.65 × 10−3 | 1.34 × 10−2 | ||
|
| |||||||||
| rs950776 | CHRNB4 | Male | 0.33 | 1.28 (0.43–3.82) | 1.22 (0.47–3.16) | 0.75 (0.30–1.85) | 0.73 (0.26–2.06) | 7.77 × 10−1 | 8.67 × 10−1 |
| Female | 0.35 | 3.29 (1.00–10.88) | 0.41 (0.17–0.97) | 0.38 (0.10–1.44) | 2.46 (0.85–7.11) | 3.42 × 10−3 | 2.11 × 10−2 | ||
|
| |||||||||
| rs7178270 | CHRNA3;CHRNB4 | Male | 0.37 | 0.97 (0.33–2.88) | 1.45 (0.53–3.94) | 0.79 (0.31–1.97) | 1.11 (0.39–3.14) | 8.46 × 10−1 | 9.29 × 10−1 |
| Female | 0.42 | 2.83 (0.75–10.66) | 0.31 (0.13–0.75) | 0.25 (0.07–0.97) | 1.64 (0.56–4.76) | 4.24 × 103 | 2.56 × 10−2 | ||
|
| |||||||||
| rs7543174b | CHRNB2 | Male | 0.14 | 0.31 (0.06–1.48) | 2.20 (0.80–6.06) | 1.53 (0.57–4.12) | 1.71 (0.56–5.23) | 1.37 × 10−1 | 3.35 × 10−1 |
| Female | 0.18 | 4.07 (1.41–11.75) | 0.76 (0.30–1.93) | 0.15 (0.02–1.22) | 0.92 (0.31–2.69) | 7.61 × 10−3 | 3.14 × 10−2 | ||
|
| |||||||||
| rs7539745b | CHRNB2 | Male | 0.13 | 0.61 (0.16–2.37) | 3.10 (1.08–8.91) | 1.37 (0.49–3.83) | 1.81 (0.59–5.59) | 2.80 × 10−1 | 4.55 × 10−1 |
| Female | 0.15 | 4.54 (1.56–13.25) | 0.65 (0.24–1.79) | 0.19 (0.02–1.54) | 1.18 (0.40–3.49) | 7.55 × 10−3 | 3.17 × 10−2 | ||
All models were adjusted for age and FTND.
SNPs above the dashed line have adjusted P-values < 0.05 within males. SNPs below the dashed line have adjusted P-values < 0.05 within females.
a
Observed P-values were obtained using a 3-df test of the gene-treatment interaction effect. P-values were adjusted for the correlation of individual contributions to score statistics for the 3-df tests within respective gene regions.
b
Adjusted SNP × Treatment × Gender Interaction P-value < 0.05