325 as the reference panel. After imputation, we obtained good-quality genotype dosage information for nine CYP2A6 variants (info score > 0.5; Supplemental Table 2), including three independent genome-wide significant SNPs identified by the NMR GWAS8 and six functional CYP2A6 alleles from the Human Cytochrome P450 Allele Nomenclature (inclusion criteria for the definition of functional CYP alleles are available at http://www.cypalleles.ki.se/criteria.htm). The final WHI sample size was 3,401 nicotine-exposed and 3,245 nicotine-unexposed individuals. For the LLFS cohort, genotyping was conducted using the Illumina HumanOmni2.5. We applied the same criteria for quality control and imputation as previously applied to the WHI cohort. Because LLFS cohorts includes related individuals, we used the PC-AiR (Principal Components Analysis in Related Samples) algorithm in the R Package GENESIS (available at https://bioconductor.org/packages/release/bioc/html/GENESIS.html) for the principal component analysis. After quality control, the final LLFS sample size was 2,077 nicotine-exposed and 2,548 nicotine-unexposed individuals – substantially smaller than the discovery sample.
