Replication was sought from cohorts participating in the Gene-Lifestyle Interactions Working Group of CHARGE. The common and three low frequency CHRNA5 variants were assessed in 12 independent replication datasets with smoking phenotypes and exome chip genotypes. Cigarettes smoked per day (CPD) was used to define the outcome because FTND scores were not available. Our replication analyses compared heavy smokers (CPD>20) to light smokers (CPD≤10). Previous work has demonstrated that these thresholds of CPD are reasonable proxies for nicotine dependence and non-dependence defined by FTND.3,26 European and African Americans were examined in separate logistic regression models that were similar to the primary sample models without the rare variant term. Specifically, the primary replication model was logit(p)=β0+βG1rs16969968+βG2LowFrequencyTerm+βCC and the secondary replication model was logit(p)=β0+βG1rs16969968+βG2rs2229961βG3rs80087508+βG3rs79109919+βCC, where C is the vector of standard covariates. For both ancestry groups, each replication study was required to have at least 50 light and 50 heavy smokers to be included in analyses of that group.
