Gene Mutation Can Raise Risk of Alcohol and Drug Abuse


An interplay between genetic and early environmental factors contributes to the development of substance abuse.

Genes DNA

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Exposure to adversities, such as parental divorce, during childhood and adolescence may increase the risk of substance abuse in persons with a particular gene mutation.

Researchers at the University of Oklahoma College of Medicine focused on a common variant of the gene for the enzyme catechol‐O‐methyltransferase (COMT, Val158Met, rs4680) in their study, which was published in Alcoholism: Clinical and Experimental Research.1

Persons with this mutation of the COMT gene are more vulnerable to the effects of stress in their early lives. The heightened vulnerability often leads to the consumption of alcohol and drugs before the age of 15 years, which is one of the key independent predictors of addiction.

“Early-life adversity doesn’t make everyone an alcoholic,” said senior study author William R. Lovallo, PhD, Professor of Psychiatry and Behavioral Sciences, OU College of Medicine, Oklahoma City, OK, in a press statement.2 “But this study showed that people with this genetic mutation are going to have a higher risk for addiction when they had a stressful life growing up.”

The study included 480 healthy young adults (average age, 23.5 years; 50% females), who had experienced no, one, or two or more types of early-life adversity during childhood and adolescence. The participants provided information on their use of alcohol and recreational drugs, and they were genotyped for the Val158Met polymorphism.

Exposure to early-life adversity was an independent predictor of earlier age at first drink (F=14.2; P<.0001). This effect was larger in Met‐allele carriers (F=13.95; P<.00001) and smaller in Val homozygotes (F=4.14; P=.02). The effects of early-life adversity on recreational drug use were similar.

These results point to an interplay between the COMT 158Met allele and early environmental factors that contributes to the development of alcohol and drug abuse.

“There is no such thing as a gene for addiction, but there are genes that respond to our environment in ways that put us at risk,” said Dr Lovallo. “You have to have the right combination to develop the risk factors.”


1. Lovallo WR, Cohoon AJ, Sorocco KH, et al. Early-life adversity and blunted stress reactivity as predictors of alcohol and drug use in persons with COMT (rs4680) Val158Met genotypes. Alcohol Clin Exp Res. 2019;43:1519-1527. doi: 10.1111/acer.14079.

2. Researcher discovers gene mutation that contributes to addiction [press release]. Oklahoma City, OK: University of Oklahoma College of Medicine; August 16, 2019.

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