There were a total of 15 cohorts included in the EUR meta-analysis (N cases = 20,923, N controls = 26,961), 4 cohorts included in the AFR meta-analysis (N cases = 5,293, N controls = 4,938), and 1 cohort included in the EAS GWAS (N cases = 2,007, N controls = 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 =1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis; Supplemental Tables 2 and 3). Using a lifetime prevalence of 24% (Breslau, Johnson, Hiripi, & Kessler, 2001), we estimated the liability scale SNP-heritability of DSM-NicDep to be 0.07 (SE = 0.01) in the EUR samples. The estimated liability scale SNP-heritability was similar in the AFR samples, but with a much larger standard error (SNP-h 2 = 0.08, SE = 0.09).