Table 1.
SNP associations in the novel DNMT3B gene and previously reported genes that were identified at P<5×10−7 in the nicotine dependence GWAS meta-analysis. The SNP with the smallest nicotine dependence GWAS meta-analysis P is shown, along with nearby SNPs previously reported in other GWAS of smoking phenotypes. Results from the UK Biobank heavy vs never smoking GWAS are also presented.
| Chr | Gene/nearest gene | Prior GWAS reported smoking phenotype | SNP (allele) | Nicotine dependence meta-analyses among ever regular smokers | UK Biobank heavy vs never smokers (N=48,931)24 | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| EUR studies (N=28,677) | AA studies (N=9,925) | EUR and AA studies (N=38,602) | |||||||||
| β (SE) | P | β (SE) | P | β (SE) | P | β (SE) | Pa | ||||
| 20q11 | DNMT3B | None | rs910083 (C) | 0.027 (0.0065) | 4.2×10−5 | 0.047 (0.012) | 7.3×10−5 | 0.032 (0.0057) | 3.7×10−8 | 0.048 (0.014) | 3.6×10−4 |
| NOL4L | Heavy vs never smoking24 | rs57342388 (CACGG) | 0.021 (0.0075) | 0.0059 | 0.032 (0.020) | 0.10 | 0.022 (0.0070) | 0.0017 | 0.094 (0.016) | 4.7×10−9 | |
| 20q13 | CHRNA4 | None | rs6062901b (G) | 0.043 (0.0088) | 8.3×10−7 | 0.022 (0.010) | 0.035 | 0.034 (0.0067) | 3.0×10−7 | 0.048 (0.018) | 0.0075 |
| Nicotine dependence23 | rs2273500b (C) | 0.046 (0.0098) | 2.0×10−6 | 0.0085 (0.016) | 0.59 | 0.036 (0.0083) | 1.6×10−5 | 0.091 (0.019) | 1.4×10−6 | ||
| Heavy vs never smoking24 | rs11697662b (C) | 0.033 (0.0085) | 9.4×10−5 | 0.013 (0.011) | 0.20 | 0.025 (0.0066) | 1.2×10−4 | 0.091 (0.017) | 1.0×10−7 | ||
| 9q 34 | DBH | None | rs56116178c (G) | 0.053 (0.010) | 4.5×10−7 | NA | NA | 0.053 (0.010) | 4.5×10−7 | 0.097 (0.022) | 9.3×10−6 |
| Heavy vs never smoking24 | rs111280114c (G) | 0.052 (0.010) | 6.4×10−7 | NA | NA | 0.052 (0.0098) | 2.5×10−5 | 0.099 (0.022) | 6.0×10−6 | ||
| Smoking cessation17 | rs3025343c (A) | 0.043 (0.0099) | 1.7×10−5 | NA | NA | 0.042 (0.0098) | 2.5×10−5 | 0.091 (0.021) | 1.1×10−5 | ||
NA, not available due to minor allele frequency <1%.
P-values correspond to genomic control being applied.
Rs2773500 and rs11697662 were originally implicated in EUR studies, where they exist in moderate LD (r2=0.64 and D′=0.95 in 1000G EUR). Rs6062901 had r2=0.47–0.57 and D′=0.73–0.84 with rs2273500 and rs11697662 in 1000G EUR and r2=0.11–0.51 and D′=0.72–0.92 in 1000G AFR.
rs56116178 and rs111280114 had r2=0.98 and D′=1 with one another and r2=0.72–0.73 and D′=0.96 with rs3025343 in 1000G EUR.