rs1880676

This family-based association study examined 14 SNPs in the choline acetyltransferase (ChAT) gene in 2,037 subjects from 602 families of African American (AA) or European American (EA) origin for association with nicotine dependence measured by smoking quantity (SQ), heaviness of smoking index (HSI), and Fagerström Test for Nicotine Dependence (FTND). Haplotype-based analysis revealed significant associations: haplotypes G-G-A-C (rs1880676-rs3810950-rs10082479-rs8178990, P=0.005-0.0178) and G-G-T-C-G-C (rs1880676-rs3810950-rs10082479-rs8178990-rs3793790-rs12266458, P=0.00247-0.00468) were significantly associated with all three ND measures in the AA sample, while haplotype T-C-G-A-T (rs12266458-rs11101191-rs8178991-rs4838544-rs4838547, P=0.00741-0.0103) showed significant association in the EA sample.

This Bayesian pharmacogenetic analysis of a bupropion vs placebo smoking cessation trial (n=436 European ancestry participants) identified four SNPs with pharmacogenetic relevance from 59 candidate SNPs in nicotinic acetylcholine receptor genes. The strongest signal was rs871058 in CHRNA5, which showed treatment-by-SNP interaction effects on 7-day smoking cessation rates. Bayesian hypothesis testing proved more conservative than unadjusted frequentist tests but less so than multiplicity-corrected tests, with no control SNPs showing significant associations.