Smoking is the most important preventable lifestyle risk factor for many diseases, including cancers [3, 54], heart disease [4, 55] and many respiratory diseases such as COPD [1, 2]. Not initiating is the best way to prevent smoking-related diseases and genetics can play a considerable part in smoking behaviours including initiation. We have performed the largest exome-wide genetic association study of smoking behaviour-related traits to date involving up to 622,409 individuals, and identified and replicated five associations, including two on the X-chromosome (Table 1). We identified a further 35 novel associations in a meta-analysis of discovery and replication cohorts (Table 2). We validated 14 previously reported SNV-smoking trait associations (Supp. Table 3) and identified secondary independent associations at three loci, including three in the 19q13 region (rs8102683, rs28399442, and rs3865453; Table 3).
