Sequencing identified 26 coding variants in CHRNA5, including 2 frameshift deletions and 24 nonsynonymous variants (details of these variants are in Figure 1 and Supplementary Table S1). The majority were predicted to be deleterious using a consensus protein prediction method.21 Interestingly, the well-studied rs16969968 variant was predicted to be neutral, supporting our approach of including all coding variants in the analyses.