Table 3.
Gender stratified SNP × treatment interaction results at end of treatment
| 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 | 1.38 (0.44–4.30) | 2.31 (0.77–6.96) | 3.07 (1.11–8.47) | 0.17 (0.07–0.45) | 7.01 × 10−5 | 1.05 ×10−3 |
| Female | 0.44 | 0.40 (0.14–1.13) | 0.64 (0.28–1.49) | 0.67 (0.25–1.84) | 1.82 (0.63–5.24) | 2.15 × 10−1 | 7.70 × 10−1 | ||
|
| |||||||||
| rs806369b | CNR1 | Male | 0.31 | 3.53 (1.23–10.09) | 1.33 (0.57–3.10) | 3.11 (1.33–7.27) | 0.30 (0.11–0.79) | 5.56 × 10−4 | 7.08 × 10−3 |
| Female | 0.3 | 0.35 (0.11–1.06) | 0.87 (0.39–1.93) | 0.68 (0.26–1.80) | 1.83 (0.73–4.57) | 1.29 × 10−1 | 6.27 × 10−1 | ||
|
| |||||||||
| rs10107450 | CIIRNA6 | Male | 0.23 | 2.11 (0.81–5.49) | 2.43 (1.02–5.80) | 0.34 (0.14–0.80) | 0.62 (0.25–1.53) | 3.09 × 10−3 | 9.66 × 10−3 |
| Female | 0.22 | 0.69 (0.23–2.03) | 0.87 (0.39–1.95) | 0.72 (0.27–1.92) | 0.62 (0.23–1.69) | 9.61 × 10−1 | 9.61 × 10−1 | ||
|
| |||||||||
| rs7017612 | CHRNA6;CHRNB3 | Male | 0.21 | 0.91 (0.33–2.47) | 2.27 (0.96–5.34) | 0.24 (0.10–0.59) | 0.92 (0.37–2.28) | 3.94 × 10−3 | 1.16 × 10−2 |
| Female | 0.18 | 0.68 (0.22–2.13) | 0.61 (0.25–1.47) | 0.80 (0.29–2.21) | 0.43 (0.14–1.29) | 8.66 × 10−1 | 9.70 × 10−1 | ||
|
| |||||||||
| rs878887 | CRHR1 | Male | 0.22 | 2.25 (1.07–4.74) | 2.03 (0.98–4.23) | 0.40 (0.19–0.85) | 0.68 (0.31–1.50) | 1.24 × 10−3 | 1.31 × 10−2 |
| Female | 0.2 | 0.30 (0.09–1.07) | 1.07 (0.47–2.44) | 0.57 (0.23–1.39) | 0.84 (0.37–1.94) | 3.40 × 10−1 | 5.82 × 10−1 | ||
|
| |||||||||
| rs2072661 | CHRNB2 | Male | 0.26 | 0.26 (0.09–0.74) | 0.33 (0.13–0.80) | 1.30 (0.59–2.85) | 2.14 (0.87–5.24) | 2.00 × 10−3 | 1.68 × 10−2 |
| Female | 0.22 | 0.71 (0.23–2.20) | 0.54 (0.22–1.29) | 1.35 (0.51–3.57) | 0.37 (0.14–1.00) | 3.02 × 10−1 | 7.64 × 10−1 | ||
|
| |||||||||
| rs2304297 | CHRNA6 | Male | 0.24 | 2.11 (0.81–5.49) | 2.30 (0.97–5.45) | 0.44 (0.20–1.01) | 0.59 (0.24–1.48) | 1.17 × 10−2 | 2.86 × 10−2 |
| Female | 0.22 | 0.88 (0.31–2.52) | 0.96 (0.43–2.14) | 0.72 (0.27–1.92) | 0.55 (0.20–1.48) | 8.42 × 10−1 | 9.60 × 10−1 | ||
|
| |||||||||
| rs11575553 | DDC | Male | 0.1 | 2.27 (0.74–6.94) | 15.33 (3.18–74.04) | 0.67 (0.22–2.11) | 0.88 (0.32–2.42) | 1.74 × 10−3 | 2.89 × 10−2 |
| Female | 0.11 | 0.32 (0.07–1.50) | 1.59 (0.61–4.16) | 1.31 (0.42–4.12) | 0.71 (0.20–2.46) | 2.68 × 10−1 | 9.28 × 10−1 | ||
|
| |||||||||
| rs2267366 | PRKCABP | Male | 0.13 | 1.17 (0.43–3.15) | 0.56 (0.23–1.36) | 0.53 (0.21–1.38) | 4.39 (1.61–11.94) | 5.38 × 10−1 | 2.93 × 10−2 |
| Female | 0.16 | 1.39 (0.57–3.42) | 0.85 (0.41–1.77) | 0.36 (0.08–1.57) | 1.25 (0.54–2.92) | 3.41 × 10−1 | 7.06 × 10−1 | ||
|
| |||||||||
| rs1876828 | CRHR1 | Male | 0.22 | 2.19 (1.01–4.74) | 2.07 (0.98–4.38) | 0.45 (0.21–0.96) | 0.63 (0.26–1.54) | 3.34 × 10−3 | 3.20 × 10−2 |
| Female | 0.21 | 0.30 (0.09–1.08) | 0.89 (0.38–2.08) | 0.49 (0.19–1.28) | 0.90 (0.39–2.09) | 3.90 × 10−1 | 6.18 × 10−1 | ||
|
| |||||||||
| rs356165 | SNCA | Male | 0.38 | 0.86 (0.30–2.45) | 0.95 (0.39–2.30) | 2.50 (1.03–6.06) | 0.22 (0.08–0.61) | 4.54 × 10−3 | 4.27 × 10−2 |
| Female | 0.41 | 0.93 (0.29–2.95) | 2.38 (0.87–6.54) | 1.21 (0.42–3.52) | 0.88 (0.34–2.28) | 4.88 × 10−1 | 9.75 × 10−1 | ||
|
| |||||||||
| rs17690326 | CRHR1 | Male | 0.22 | 2.02 (0.96–4.23) | 1.58 (0.78–3.19) | 0.41 (0.19–0.85) | 0.67 (0.31–1.47) | 5.53 × 10−3 | 4.84 × 10−2 |
| Female | 0.2 | 0.30 (0.08–1.05) | 1.09 (0.48–2.49) | 0.48.0 (20–1.18) | 0.85 (0.37–1.94) | 2.61 × 10−1 | 4.78 × 10−1 | ||
|
| |||||||||
| Significant SNPs within Females | |||||||||
| rs950776 | CHRNB4 | Male | 0.33 | 1.65 (0.64–4.24) | 1.37 (0.56–3.31) | 0.69 (0.31–1.53) | 0.55 (0.23–1.35) | 2.62 × 10−1 | 7.68 × 10−1 |
| Female | 0.35 | 1.71 (0.58–5.02) | 0.38 (0.17–0.87) | 0.49 (0.18–1.30) | 3.61 (1.34–9.74) | 1.52 × 10−3 | 1.09 × 10−2 | ||
|
| |||||||||
| rs871058 | CHRNA5 | Male | 0.33 | 1.21 (0.47–3.11) | 0.89 (0.37–2.12) | 0.69 (0.31–1.53) | 0.41 (0.17–1.01) | 4.07 × 10−1 | 9.17 × 10−2 |
| Female | 0.37 | 1.31 (0.45–3.86) | 0.24 (0.10–0.55) | 0.59 (0.22–1.56) | 2.44 (0.95–6.28) | 1.78 × 10−3 | 1.24 × 10−1 | ||
|
| |||||||||
| rs514743 | CHRNA3;CHRNA5 | Male | 0.35 | 1.00 (0.39–2.55) | 1.16 (0.49–2.77) | 0.49 (0.21–1.09) | 0.51 (0.21–1.25) | 3.80 × 10−1 | 8.98 × 10−1 |
| Female | 0.39 | 1.07 (0.36–3.15) | 0.35 (0.15–0.81) | 0.69 (0.26–1.83) | 3.96 (1.40–11.23) | 2.79 × 10−3 | 1.87 × 10−2 | ||
|
| |||||||||
| rs9610375 | MAPK1 | Male | 0.49 | 0.78 (0.26–2.37) | 0.87 (0.33–2.29) | 0.76 (0.31–1.84) | 0.59 (0.20–1.76) | 9.65 × 10−1 | 9.65 × 10−1 |
| Female | 0.48 | 0.56 (0.19–1.64) | 0.38 (0.16–0.88) | 6.54 (1.38–30.93) | 0.66 (0.25–1.71) | 3.48 × 10−3 | 2.01 × 10−2 | ||
|
| |||||||||
| rs4275821 | CHRNA5 | Male | 0.35 | 1.25 (0.48–3.24) | 0.89 (0.37–2.12) | 0.71 (0.32–1.57) | 0.47 (0.19–1.16) | 5.14 × 10−1 | 9.67 × 10−1 |
| Female | 0.38 | 1.10 (0.37–3.23) | 0.27 (0.12–0.62) | 0.54 (0.20–1.44) | 2.58 (0.98–6.79) | 3.49 × 10−3 | 2.29 × 10−2 | ||
|
| |||||||||
| 18737865b | COMT | Male | 0.31 | 0.70 (0.34–1.44) | 1.13 (0.55–2.31) | 0.72 (0.38–1.33) | 2.11 (1.11–4.01) | 5.70 × 10−2 | 4.22 × 10−1 |
| Female | 0.28 | 1.25 (0.58–2.70) | 1.86 (0.92–3.73) | 0.64 (0.30–1.36) | 0.28 (0.12–0.67) | 3.23 × 10−3 | 3.71 × 10−2 | ||
|
| |||||||||
| rs3743075 | CHRNA3 | Male | 0.35 | 1.27 (0.49–3.25) | 1.09 (0.46–2.61) | 0.52 (0.23–1.17) | 0.51 (0.21–1.25) | 3.37 × 10−1 | 8.60 × 10−1 |
| Female | 0.38 | 1.11 (0.37–3.26) | 0.32 (0.14–0.73) | 0.50 (0.19–1.34) | 2.66 (1.01–7.02) | 6.41 × 10−3 | 3.92 × 10−2 | ||
|
| |||||||||
| rs1063311 | MAPK1 | Male | 0.46 | 0.83 (0.43–1.62) | 0.84 (0.46–1.52) | 1.37 (0.77–2.45) | 0.73 (0.36–1.46) | 4.82 × 10−1 | 8.10 × 10−1 |
| Female | 0.43 | 0.77 (0.38–1.56) | 0.61 (0.34–1.09) | 3.08 (1.36–6.98) | 0.97 (0.53–1.80) | 8.76 × 10−3 | 4.44 × 10−2 | ||
|
| |||||||||
| rs2266966 | MAPK1 | Male | 0.46 | 0.83 (0.43–1.62) | 0.80 (0.44–1.45) | 1.38 (0.77–2.45) | 0.73 (0.36–1.46) | 4.56 × 10−1 | 7.89 × 10−1 |
| Female | 0.43 | 0.81 (0.40–1.62) | 0.60 (0.33–1.07) | 3.08 (1.36–6.98) | 0.97 (0.53–1.80) | 8.72 × 10−3 | 4.44 × 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.