Genetic Variations Between Alcohol Consumption and Alcohol Use Disorder

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The Alcohol Use Disorders Identification Test measures consumption and problematic consequences of drinking to determine hazardous alcohol use.
The Alcohol Use Disorders Identification Test measures consumption and problematic consequences of drinking to determine hazardous alcohol use.

The findings of a meta-analysis published in the American Journal of Psychiatry pointed to several genes associated with alcohol misuse, some of which suggest genetic differences between heavy alcohol use and alcohol use disorder.

Twin studies have established that alcohol use disorders are "moderately heritable." Certain genes, such as ADH1B, ADH1C, KLB, and GCKR, have been associated with alcohol consumption, although not necessarily dependence.

The authors performed a meta-analysis of genome-wide association studies of 2 population-based cohorts of European ancestry (UK Biobank [n=121,604], 23andMe [n=20,328]).

Alcohol Use Disorders Identification Test (AUDIT) scores, a measure that includes scores representing consumption (AUDIT-C, questions 1-3) and problematic consequences of drinking (AUDIT-P, questions 7-10), were available for these individuals.

The authors discovered several relationships between these scores and specific genetic variants.

First, they found associations similar to those of previous studies, including KLB, GCKR, and CADM2, plus novel associations, such as JACD and SLC39A8, with single nucleotide polymorphism heritability between 9% and 12%. Not all genes associated with AUDIT-P scores were associated with AUDIT-C scores, which suggests that vulnerabilities to alcohol misuse, as opposed to alcohol consumption, may be identified in future studies.

High scores in the "problematic consequences" category of AUDIT were associated with psychiatric illness compared with high consumption scores alone, which further reflects a difference between drinking behaviors and alcohol use disorders.

One limitation of the study was that the AUDIT captures only a year of a respondent's life, which means scores may not have reflected stable genetic traits.

Reference

Sanchez-Roige S, Palmer A, Fontanillas P, et al. Genome-wide association study meta-analysis of the Alcohol Use Disorders Identification Test (AUDIT) in two population-based cohorts [published online October 19, 2018]. Am J Psychiatry. doi: 10.1176/appi.ajp.2018.18040369

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