The top novel nicotine dependence-associated variant was tested for association with lung cancer using 27,349 cases and 54,472 controls from >30 EUR studies in the Transdisciplinary Research for Cancer in Lung of the International Lung Cancer Consortium (TRICL-ILCCO). Their genotyping, quality control, 1000G imputation, and statistical analyses were previously described.39 Briefly, the SNP associations were derived from a meta-analysis of logistic regression model results that compared lung cancer cases and controls, adjusting for age, sex, and the first two principal components. Histological subtypes of adenocarcinoma and squamous cell lung carcinoma cases were compared, separately, to controls. We removed the EAGLE study from the original set of lung cancer studies to avoid overlap in the nicotine dependence and lung cancer meta-analyses. All lung cancer analyses included ever- and never-smokers; our follow-up association testing made additional adjustments for smoking history (ever vs never) and pack-years.
