For top nicotine dependence-associated SNPs, we performed in silico testing of their associations with lung cancer using 1000 Genomes–imputed GWAS meta-analysis results generated elsewhere.47 CHRNA4 SNP results were provided using 12 160 cases and 16 838 controls from six samples of European-ancestry: the International Agency for Research on Cancer,48 Institute of Cancer Research,49 MD Anderson Cancer Center,50 National Cancer Institute (comprising EAGLE and the Prostate, Lung, Colon and Ovary Study Cancer Screening Trial),51 Samuel Lunenfeld Research Institute in Toronto51 and Helmholtz-Gemeinschaft Deutscher Forschungszentren in Germany.51 SNP associations, adjusted for age, sex and the first two principal component eigenvectors, were evaluated using all lung cancer cases and controls and using subsets of 3718 adenocarcinoma and 3422 squamous cell carcinoma cases. SNP associations with lung cancer were also tested with adjustment for smoking history (ever vs never) and pack-years of smoking among ever smokers (0 for never smokers) in three of the case–control samples, which together comprised 16% never smokers and 84% ever smokers.
