Recent progress in GWAS of AUD has identified several variants across many loci that are significantly associated with alcoholism and related traits (Table 2). Some variants in these loci result in amino acid changes (e.g. rs1229984 in ADH1B) and known to alter the function of the gene to affect outcome of AUD. Most other AUD and alcohol consumption associated variants occur in intergenic or intronic regions and are not directly associated with protein coding changes[65]. Linkage disequilibrium (LD) at many loci span across thousands of variants and further makes it difficult to identify a causal SNP or genes associated with the disorder[66]. Thus, many AUD GWAS just annotated the nearest gene to the lead SNP as the susceptibility loci (Table 2). Furthermore, due to different LD structure across datasets, many times individual study identified different lead SNPs and/ or different nearest genes within the same loci. Recent studies on psychiatric and neurological disorders showed that the most of genome-wide significant variants occur on active enhancers or promoters and might alter the expression level of nearby (cis) or distant (trans) gene[66–68].
