Summary: Researchers have identified 29 genes linked to problematic alcohol use. The new international study shows that, in addition to a higher risk of alcohol use disorder, people carrying certain risk variants also have an elevated genetic predisposition to depression, insomnia, and nicotine and drug dependence.
Source: Aarhus University
If you struggle with problematic alcohol use, your genes may also increase your statistical risk for depression, insomnia and dependence on tobacco and other substances. New international research involving iPSYCH researchers from Aarhus University reveals these genetic connections.
The study set out to clarify how inherited genetic variation contributes to long-term patterns of heavy drinking that cause significant psychological, social and physical harm. Given that problematic alcohol use is a major driver of disease, premature death and social difficulties across many populations, understanding genetic risk factors is a central goal for researchers aiming to improve prevention and treatment.
For years scientists have worked to identify the genetic variants that raise the risk of alcohol dependence and related harmful drinking. Previously, about ten genetic variants had been reliably associated with problematic alcohol use. This new analysis, published in Nature Neuroscience, increases that number to 29 independent risk variants.
The study is the result of an international collaboration including research teams from the United States, United Kingdom, Germany, Sweden and Denmark. Danish contributors include Associate Professor Mette Nyegaard and Professor Anders D. Børglum from the Department of Biomedicine at Aarhus University, representing the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH).
Fine-combing large databases
To find these risk variants the researchers systematically analysed genomic data from a very large sample, explains Associate Professor Mette Nyegaard. The study combined genetic profiles and health information for 435,563 individuals of European ancestry drawn from major resources: the UK Biobank, the US Million Veteran Program, and the Psychiatric Genetics Consortium.
Millions of genetic variants were compared across participants with and without problematic alcohol use. The goal was to identify variants that were significantly more common among those with problematic drinking or alcohol use disorder. After locating these risk variants, the research team compared the genetic pattern for problematic alcohol use with genetic patterns linked to many other traits and disorders.
- The analysis showed a strong genetic relationship between problematic alcohol use and a wide range of psychiatric illnesses.
- It also revealed shared genetic risk with other forms of substance use, including drug dependence and tobacco smoking.
The genetic overlap with psychiatric disorders is notable because it is not seen for general measures of alcohol consumption. In other words, the genetics underlying problematic, harmful alcohol use differ from the genetics that influence typical levels of drinking, highlighting important distinctions between ordinary consumption and clinically significant alcohol problems.
“We are beginning to outline a genetic architecture linking alcohol misuse to other substance use and to psychiatric conditions such as ADHD and depression,” says Mette Nyegaard. She emphasizes that genes are only part of the story: environmental factors, life experiences and social context also play a major role in whether someone develops problematic alcohol use.
The newly identified risk genes offer insight into the biological pathways that may contribute to the development of alcohol-related disorders. This biological understanding could, over time, inform the design of new treatments aimed at reducing or eliminating alcohol dependence.
While it remains uncertain whether any of the 29 identified variants will directly yield effective new medications, the study notes that 16 of the implicated genes are known drug targets—meaning they can be influenced by existing pharmaceutical compounds. This raises possibilities for repositioning or investigating drugs that act on these targets.
In addition to substance-related traits, the study found a genetic relationship between problematic alcohol use and insomnia, further illuminating the complex set of traits that share genetic liability with alcohol problems.
About this neuroscience research article
Source:
Aarhus University
Media Contacts:
Mette Nyegaard – Aarhus University
Image Source:
The image is in the public domain.
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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