SH3BP5-NR2C2 region contains five known genes including SH3BP5, CAPN7, ZFYVE20, MRPS25 and NR2C2, all of which except MRPS25 were enriched with replicable risk SNPs. Thirty, 34 and 35 SNPs in this region were nominally associated with alcohol and nicotine co-dependence in EAs (2.5×10-5≤p≤0.038), AAs (9.3×10-4≤p≤0.046) and meta-analysis (4.1×10-7≤p≤0.049), respectively. Among them, 11 SNPs were replicable across EAs and AAs and became more significant in meta-analysis (4.1×10-7≤p≤4.1×10-3) (Table 1). Effects of all of these 11 SNPs were in the same direction between two populations. These 11 SNPs were located in two haplotype blocks, i.e., ZFYVE20-NR2C2 (block 1) and SH3BP6-CAPN7 (block 2) (Figure 1d). Minor alleles of all replicable SNPs in block 2 increased risk for disease (OR>1 in both EAs and AAs, and Z score > 0 in meta-analysis), but minor alleles in block 1 protected against disease (OR<1 in both EAs and AAs, and Z score < 0 in meta-analysis). The -log(p) values for all available SNPs across SH3BP5-NR2C2 region were plotted in Figure 1. The distributions of -log(p) values were consistent across EAs, AAs, and meta-analysis (0.315≤r≤0.868; 8.1×10-52≤p≤3.6×10-5; Table 2).
