ANAPC1 and SLCO3A1 are associated with nicotine dependence: meta-analysis of genome-wide association studies.

Twin and family studies have shown that there is substantial evidence for a genetic component in the vulnerability to nicotine dependence (ND). The purpose of this study was to perform a meta-analysis on two genome-wide association (GWA) data involving 1079 cases of ND and 1341 controls in Caucasian populations. Through meta-analysis we identified 50 SNPs associated with ND with p<10(-4). The best associated SNP rs7163369 (p=3.27×10(-6)) was located at 15q26 within SLCO3A1 gene while the second best SNP was rs9308631 (p=9.06×10(-6)) at 2q12.1 near ANAPC1. The third interesting locus rs688011 (p=1.08×10(-5)) was at 11q23.2 intergenic between NCAM1 and TCC12. Through meta-analysis, we found two additional ND associated genes ZCCHC14 (the top SNP was rs13334632, p=1.28×10(-5)) and KANK1 (the top SNP was rs13286166, p=1.49×10(-5)). The first top SNP rs7163369 within SLCO3A1 in the meta-analysis was replicated in the Australian twin-family study of 778 families (p=6.11×10(-5)) while SNP rs9653414 within ANAPC1 (p=4.61×10(-5)) in the meta-analysis was replicated in the family sample (p=9.31×10(-4)). Furthermore, rs2241617 in ZCCHC14 and rs4742225 in KANK1 showed strong associations with ND (p=1.06×10(-7) and 4.81×10(-7), respectively) in the replication sample. In addition, several SNPs of these loci (ANAPC1, KANK1, NACM1, TCC12, SLCO3A1 and ZCCHC14) were associated with alcohol dependence. In conclusion, we identified several loci associated with ND through meta-analysis of two GWA studies. These findings offer the potential for new insights into the pathogenesis of ND.

1,079 European ancestry cases, 1,341 European ancestry controls