Summary: Researchers have identified 29 genetic variants linked to problematic alcohol use. Nineteen of the genes were previously unknown independent risk factors for alcohol use disorder.
Source: Yale
A genome-wide analysis of more than 435,000 people has identified 29 genetic variants linked to problematic drinking, researchers at Yale University School of Medicine and colleagues report May 25 in the journal Nature Neuroscience.
“The new data triple the number of known genetic risk loci associated with problematic alcohol use,” said Yale’s Joel Gelernter, the Foundations Fund Professor of Psychiatry and professor of genetics and of neuroscience, who is the senior author of the multi-institutional study.
The study includes genome-wide analysis of people of European ancestry contained in four separate biobanks or datasets. The researchers looked for shared genetic variants among those who met criteria for problematic alcohol use, including alcohol use disorder and alcohol use with medical consequences. These disorders are major contributors to a wide variety of medical problems worldwide.
The analysis found 19 previously unknown independent genetic risk factors for problematic alcohol use, and confirmed 10 previously identified risk factors.
The meta-analysis of biobank data also included information on genetic risk factors for several psychiatric disorders. This information allowed researchers to study shared genetic associations between problematic drinking and disorders such as depression and anxiety.
They also found genetic heritability of these variants was enriched in the brain and in evolutionarily conserved regulatory regions of the genome, attesting to their importance in biological function. Using a technique called Mendelian randomization, they were able to investigate how one genetically influenced trait affects another genetically linked trait.
“This gives us ways to understand causal relations between problematic alcohol use traits such as psychiatric states, risk-taking behavior, and cognitive performance,” said Yale’s Hang Zhou, associate research scientist in psychiatry and lead author of the study.
“With these results, we are also in a better position to evaluate individual-level risk for problematic alcohol use,” Gelernter said.
About this neuroscience research article
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Yale
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Bess Connolly – Yale
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Original Research: Closed access
“Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits”. by Hang Zhou, Julia M. Sealock, Sandra Sanchez-Roige, Toni-Kim Clarke, Daniel F. Levey, Zhongshan Cheng, Boyang Li, Renato Polimanti, Rachel L. Kember, Rachel Vickers Smith, Johan H. Thygesen, Marsha Y. Morgan, Stephen R. Atkinson, Mark R. Thursz, Mette Nyegaard, Manuel Mattheisen, Anders D. Børglum, Emma C. Johnson, Amy C. Justice, Abraham A. Palmer, Andrew McQuillin, Lea K. Davis, Howard J. Edenberg, Arpana Agrawal, Henry R. Kranzler & Joel Gelernter.
Nature Neuroscience doi:10.1038/s41593-020-0643-5
Abstract
Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits
Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. Although genome-wide association studies have identified PAU risk genes, the genetic architecture of this trait is not fully understood. We conducted a proxy-phenotype meta-analysis of PAU, combining alcohol use disorder and problematic drinking, in 435,563 European-ancestry individuals. We identified 29 independent risk variants, 19 of them novel. PAU was genetically correlated with 138 phenotypes, including substance use and psychiatric traits. Phenome-wide polygenic risk score analysis in an independent biobank sample (BioVU, n = 67,589) confirmed the genetic correlations between PAU and substance use and psychiatric disorders. Genetic heritability of PAU was enriched in brain and in conserved and regulatory genomic regions. Mendelian randomization suggested causal effects on liability to PAU of substance use, psychiatric status, risk-taking behavior and cognitive performance. In summary, this large PAU meta-analysis identified novel risk loci and revealed genetic relationships with numerous other traits.
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