Multi-ancestry study reveals shared genetics of problem drinking

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A study led by VA Connecticut Healthcare Center/Yale researchers reveals that ancestors around the world share a genetic architecture for problematic alcohol use (PAU) chronic drinking, coupled with harmful consequences.

The findings, published in Natural Medicine, will help scientists understand the genetic basis of PAU, a major cause of health problems in many age groups. It is the main cause of death for those who suffer from it.

This study is the largest to date for PAUit that has identified many new risk genes and discovered many new biology. With a better understanding of PAU biology, scientists have new possibilities to develop treatments.

Hang Zhou, Ph.D., assistant professor of psychiatry and of biomedical informatics & data science at Yale School of Medicine and VA Connecticut, and first author of the study, said, “Research with the main goal of understanding the molecular mechanisms underlying PAU and the identification of gene targets for potential pharmacological studies are extremely important for future treatments and help to reduce the consequences of excessive alcohol use.”

Researchers studied more than 1 million people with PAU and included as many genetic ancestral groups as possible, including people with European, African, Latin American, East Asian, and South Asian ancestry. ancestors.

The Million Veteran Program (MVP) is a major source of data for this study.

Compared to previous research, this work extends these findings and shows that the genetic architecture of PAU is shared by many of these populations. There are genetic differences among different populations for PAU, but the similarities are overwhelming. Cross-ancestry information allows researchers to improve the power of gene discovery.

“By using extensive genealogical information, we identified 110 gene regions and improved mapping of potential causal variants in each region,” said Zhou.

The researchers also used different methods to prioritize several genes with convergent evidence linking the association of PAU to brain biology through gene expression (study of whole transcriptional association in 13 tissues in the brain) and chromatin interaction analysis in the brain. This work will provide valuable resources and targets for future functional analysis and drug development.

Joel Gelernter, MD, Funding Professor of Psychiatry, and professor of genetics and neuroscience at the Yale School of Medicine and VA Connecticut, is the senior author of the study.

“One of the most important products of this research is the information provided about PAU risk across the genome,” Gelernter said. “The resulting data allow us to better understand the biology of PAU, suggesting some already approved drugs that can be tools for the treatment of PAU in the future, with further research. The data we have made will be shared to the research community, and it may be very helpful in the future research of other scientists.”

Drug repurposing analysis identified several drugs with potential treatment for PAU, described in the published article.

One of the outputs from this study is genome-wide association data, and this type of information can be used to compute “polygenic risk scores,” or PRS, which can be used to estimate an individual’s genetic risk for in PAU.

The researchers emphasize that the PRS they calculated is not yet ready for clinical use, but they also tested the association of the PRS for PAU with hundreds of medical characteristics in several biobanks including the Biobank of Vanderbilt University Medical Center , the BioMe of Mount Sinai, the Mass. General Brigham Biobank, and Penn Medicine Biobank. This analysis identified genetic correlations between PAU and several other mental and neurological disorders.

More information:
Hang Zhou et al, Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals, Natural Medicine (2023). DOI: 10.1038/s41591-023-02653-5

Provided by Yale University

Citation: Multi-ancestry study uncovers shared genetics of problem drinking (2023, December 22) retrieved 22 December 2023 from genetics-problematic.html

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