Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders.

December 1, 2018

Walters RK, Polimanti R, Johnson EC, McClintick JN, Adams MJ, Adkins AE, Aliev F, Bacanu SA et al.
Nat Neurosci. 2018 21(12):1656-1669. doi: 10.1038/s41593-018-0275-1. PMCID: PMC6430207

Liability to alcohol dependence (AD) is heritable, but little is known about its  complex polygenic architecture or its genetic relationship with other disorders.  To discover loci associated with AD and characterize the relationship between AD  and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant  effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10-13) and African ancestries (rs2066702; P = 2.2 × 10-9). Significant  genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.