Genetics of alcohol use disorder: a review

Abstract

Alcohol use disorder (AUD) represents a significant and ongoing public health concern with 12-month prevalence estimates of ∼5.6%. Quantitative genetic studies suggest a heritability of approximately 50% for AUD, and as a result, significant efforts have been made to identify specific variation within the genome related to the etiology of AUD. Given the limited number of replicable findings that have emerged from genome-wide linkage and candidate gene association studies, more recent efforts have focused on the use of genome-wide association studies (GWAS). These studies have suggested that hundreds of variants across the genome, most of small effect (R² < 0.002), contribute to the genetic etiology of AUD. The present review describes the initial, though limited, successes of GWAS to identify loci related to risk for AUD as well as other etiologically relevant traits (e.g. alcohol consumption). In addition, 'Post-GWAS' approaches that rely on GWAS data to estimate the heritability and co-heritability of traits, test causal relations between traits, and aid in gene discovery are described. Together, the described research findings illustrate the importance of molecular genetic research on AUD as we seek to better understand the mechanisms through which genetic variation leads to increased risk for AUD.