These findings suggest that NKAIN1-SERINC2 region might harbor a causal locus (or loci) for alcohol dependence and that the proteins encoded by NKAIN1-SERINC2 might contribute directly to the vulnerability to alcohol dependence. First, NKAIN1-SERINC2 region was the only association peak within a 10Mb region in the European-American discovery sample (threshold p=10−4). It is, thus, highly likely that the putative causal locus for alcohol dependence is located within NKAIN1-SERINC2. Second, half of the unimputed risk SNPs in this region had significant cis-acting regulatory effects on NKAIN1-SERINC2 mRNA expression, increasing the possibility that NKAIN1-SERINC2 per se plays a direct functional role in the disorder. Third, the distributions of −log(P) values for either SNP-disease associations or for SNP-expression associations were consistent across at least 8 populations, suggesting that NKAIN1-SERINC2 may contribute to the risk for alcohol dependence, and that the regulatory pathway via which these SNPs cause alcohol dependence may possibly be related to the NKAIN1-SERINC2 proteins per se.
