SNPs based on their functional consequences on enzymatic activity before they were highlighted via agnostic GWAS [85, 91]. Associations of these SNPs or their proxies on alcohol-related disease outcomes include coronary heart disease [85], various cancers [92, 93], renal function [94], blood pressure [95], and cirrhosis [96]. Beyond these functional missense SNPs, the intronic AUTS2 SNP rs6943555 was implicated as a cis-eQTL for AUTS2 in PFC [60], and the intronic KLB SNP rs11940694 was implicated as a cis-eQTL for the replication factor RCF1 gene in cerebellum [58]. Little else is known about the biological relevance of other noncoding SNPs that may exert independent effects on regulation of genes that underlie alcohol metabolism in liver or the neurobiology of developing an alcohol use disorder.
