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Yale Scientists Identify Genetic Risk Factors Associated With Habitual Heavy Drinking

October 27, 2022

A new study led by Yale scientists has identified genetic risk factors associated with habitual heavy drinking.

The study, published in JAMA Network Open, used data from the U.S. Million Veteran Program and multiple other large-scale studies of alcohol outcomes. It examined the genetic influences on maximum habitual alcohol intake (MaxAlc) to learn how this heavy drinking behavior compares to lower levels of alcohol use, alcohol dependence, and relationships with mental and physical health.

The study identified 15 genetic risk variants for heavy drinking – including genes related to alcohol metabolism along with new genetic findings such as a gene previously associated with bitter beverage taste preferences and a gene related to biomarkers of excessive alcohol use.

The authors also used genetic data to demonstrate a causal relationship between habitual heavy drinking and increased liver enzyme levels – an indicator that is valuable for detecting alcohol-related liver diseases.

The study also showed that habitual heavy drinking is genetically more similar to alcohol use disorder compared to lower levels of alcohol consumption – an important difference in distinguishing between risk for developing alcohol dependence and lower levels of nondependent alcohol use.

“We are learning that alcohol-related traits are different genetically and biologically, which is somewhat counterintuitive,” said senior author Joel Gelernter, MD, Foundations Fund Professor of Psychiatry and professor of genetics and of neuroscience. “Drinking more is not necessarily the same as drinking alcoholically … that requires also drinking habitually.”

Habitual heavy drinking was also genetically related to other mental health outcomes. The strongest relationship was with suicidality which is consistent with what is known about the relationship between alcohol intoxication and increased rates of attempting suicide.

We are learning that alcohol-related traits are different genetically and biologically, which is somewhat counterintuitive.

Joel Gelernter, MD

“It’s interesting to see these different patterns of association emerge for different levels and patterns of alcohol use and alcohol use problems,” said lead author Joseph Deak, PhD, postdoctoral fellow at Yale School of Medicine. “Clinically, drinking in moderation has different health implications compared to habitual heavy drinking and risk for developing an alcohol use disorder – and a similar story emerges using genetic data."

Overall, these findings suggest that there are key genetic distinctions between drinking alcohol in moderation versus drinking alcohol excessively in terms of relationship to risk for alcohol use disorder, psychiatric outcomes including suicidality, and long-term alcohol-related disease such as liver disease.

"What we’ve learned is that problematic drinking is complex, and the genetics reflect that complexity,” Deak said. “The genetics is helping us work out what’s really going on biologically underneath what we can see clinically.”

“And this is another example of how the Million Veteran Program is increasing our knowledge of complex genetic traits,” Gelernter said.

Other study authors from Yale include Daniel F. Levey, PhD; Frank Wendt, PhD; Hang Zhou, PhD; Marco Galimberti, PhD; and Renato Polimanti, PhD.

Submitted by Christopher Gardner on October 27, 2022