Genes may explain transition from heavy drinking to alcohol use disorder

The genetic architecture differences between alcohol consumption and alcohol use disorder (AUD) are consistent with the diverse biological contributions by the two conditions, reveals a study.

“Genetic variants with direct effects on AUD are potentially relevant to understanding the transition from heavy alcohol consumption to AUD and may be targets for translational prevention and treatment efforts,” the authors said.

Longitudinal data from the cross-ancestry Million Veteran Program sample were used to identify the following: the novel loci associated with AUD and alcohol consumption (measured by the score on the consumption subscale of the Alcohol Use Disorders Identification Test [AUDIT-C]), the impact of phenotypic variation on genetic discovery, and genetic variants with direct effects on AUD that are not mediated through alcohol consumption.

Twenty-six loci associated with AUD and 22 loci associated with AUDIT-C score, including ancestry-specific and novel ones, were identified. Secondary genome-wide association studies (GWAS) that excluded individuals reporting abstinence revealed seven additional loci for AUD and eight more for AUDIT-C score.

“Although the heterogeneity of the abstinent group biases the GWAS findings, unique variance between alcohol consumption and disorder remained after the abstinent group was excluded,” the authors said.

In mediation analysis, a set of variants with effects on AUD, which were not mediated through alcohol consumption, were found.

“Understanding the genetic factors that underlie the transition from heavy drinking to AUD has important theoretical and clinical implications,” the authors said.