The only common coding variant identified was the previously well-studied variant rs16969968 located in exon 5 of CHRNA5. In the primary sample, the rs16969968 minor allele was associated with increased risk for nicotine dependence in European (OR=1.3, p=0.003) and African Americans (OR=1.5, p=0.04) (Multivariate Model Set 1, Table 2). Replication results from 12 independent studies provide strong evidence that the A allele of rs16969968 increases risk for heaviness of smoking (Figure 2 and Supplementary Tables S2-S3). Meta-analyses combining results from the primary and replication datasets demonstrate that rs16969968 has an OR of 1.3 in both European (p=3.7×10−11) and African Americans (p=0.01).
