developing smoking-related health outcomes, including: CHRNA5 with lung cancer (most recently [34]), lung function [35], airflow obstruction [36], COPD (most recently [37]), and peripheral arterial disease [9]; the nicotine metabolizing gene CYP2A6 with lung cancer [11], lung function [35], and emphysema [38]; and CHRNB3-CHRNA6, CHRNA4, and the DNA methyltransferase gene DNMT3B with lung cancer [11, 21, 26]. Beyond common SNPs, the CHRNA5-CHRNA3-CHRNB4 [39–42] and CHRNA4 [40, 43, 44] loci also harbor smoking-associated rare variants, albeit some do not have replication evidence or occur in an isolated population. Genome-wide significant SNP associations in other loci have been reported but not yet independently replicated [8, 13, 20, 22, 24].
