Our GWAS meta-analysis tested nearly 18 million genotyped and 1000G-imputed SNPs/indels for association with mild/moderate/severe dependence (λ=1.027, Supplementary Figure 1A). We observed SNP/indel associations at meta-analysis P<5×10−8 at two loci (Figure 1): the well-known chromosome 15q25 locus spanning CHRNA5-CHRNA3-CHRNB4 (smallest meta-analysis P=1.3×10−25) and a novel chromosome 20q11 locus spanning the DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) gene (smallest meta-analysis P=3.7×10−8). No additional loci were identified at P<5×10−8 in the ancestry-specific GWAS meta-analyses (Supplementary Figures 1B–C and 2A–B).