There were a total of 15 cohorts included in the European ancestry (EUR) meta-analysis (Ncases = 20,923, Ncontrols = 26,961), four cohorts included in the African ancestry (AFR) meta-analysis (Ncases = 5,293, Ncontrols = 4,938), and one cohort included in the East Asian ancestry (EAS) GWAS (Ncases = 2,007, Ncontrols = 1,739), for a total cross-ancestry sample size of N = 61,861 (28,223 cases; Supplemental Table 1). We identified one genome-wide significant locus, near the cholinergic receptor nicotinic alpha 5 subunit (CHRNA5) gene on chromosome 15 (lead SNP: rs147144681, p-value =1.27E-11 in European ancestry; lead SNP = rs2036527, p-value = 6.49e-13 in cross-ancestry analysis; Supplemental Tables 2 & 3). Using a lifetime prevalence of 24%32, we estimated the liability scale SNP-heritability of DSM-defined nicotine dependence (DSM-NicDep) to be 0.07 (SE = 0.01) in the European ancestry samples.