TUD-EUR included 11,422,241 imputed SNPs in a cohort of 163,734 TUD cases and 331,271 controls, which is 8.5 times larger than the total sample size of previous nicotine dependence GWAS.27 Observable inflation is attributable to polygenic signal rather than population stratification or other confounding (LDSC intercept 1.049, SE=0.012) and we did not identify evidence of heterogeneity (I2) across the cohorts (Supplementary Figure 6). The TUD-EUR meta-analysis yielded a significant h2SNP estimate of 11.70% (SE=0.005, Supplementary Table 9), and identified 74 GWS significant lead SNPs located in 63 independent loci (Figure 2B; Supplementary Table 10). Fourteen of these loci were ancestry specific in EUR and not GWS in the multi-ancestry GWAS. Among the 63 independent loci, 13 were fine-mapped to a credible set (posterior inclusion probability > 0.50), of which 6 harbored known protein coding genes (CHRNB2, GALNT10, FAM168A, SPATS2, SYT17, ASIC2; Supplementary Table 11).
