We combined GWAS results, using METAL27 with fixed-effects inverse variance-weighting meta-analysis, across all studies with FTND data to maximize statistical power. Genomic control was applied to the deCODE results to adjust for inflation due to relatedness among participants; all other studies had low inflation values (λ≤1.02). We excluded SNPs/indels with minor allele frequency (MAF) <1% in 1000G EUR or African (AFR) panels, depending on the ancestry group analyzed. The standard threshold (P<5×10−8), originally based on 1 million independent tests genome-wide as computed using HapMap-based imputation for EUR studies,28 has been validated for 1000G-imputed GWAS of common variants.29 Rather than imposing a more stringent, yet to be consistently determined, threshold when analyzing common variants across EUR and AA studies,29–32 we carried forward novel variation implicated at P<5×10−8 and relied on confirmation in an independent study to declare genome-wide significance. For this confirmation step, we utilized UK Biobank (N=48,931 EUR participants) results with heavy, defined as pack-years ([CPD/20 cigarettes per pack] × years smoked) ≥10, vs never smoking as a proxy phenotype.24 This prior GWAS was designed as a nested case-control analysis that sampled the extremes of smoking behavior, and thus did not encompass light smoking.
