A new study led by researchers from the VA Connecticut Healthcare Center and Yale School of Medicine has made a significant breakthrough in understanding the genetics of problematic alcohol use (PAU).
Published in Nature Medicine, this study stands as the largest for PAU and has identified numerous risk genes, providing a deeper understanding of the condition’s biology.
Dr. Hang Zhou, the study’s first author, emphasizes the importance of understanding the molecular mechanisms underlying PAU. This knowledge is crucial for developing future treatments and mitigating the consequences of excessive alcohol use.
The researchers analyzed genetic data from over 1 million individuals with PAU, representing various genetic ancestries, including European, African, Latin American, East Asian, and South Asian.
This inclusive approach, leveraging data from the Million Veteran Program and other sources, allowed for a more comprehensive analysis.
Contrary to previous studies, the current research discovered that the genetic architecture of PAU is substantially shared across different populations. Despite some genetic variations, the similarities in genetic risk for PAU were more pronounced.
Utilizing cross-ancestry information significantly enhanced the power of gene discovery, leading to the identification of 110 gene regions and the fine-mapping of potential causal variants in each area.
Moreover, the study employed various methods to prioritize genes linking association to PAU with brain biology. These methods include gene expression analysis in 13 brain tissues and chromatin interaction analyses.
This approach will provide resources and targets for future drug development and functional analyses.
Joel Gelernter, the study’s senior author, highlighted the value of the genome-wide association data generated.
This data not only improves the understanding of PAU biology but also suggests potential repurposing of already-approved drugs for treating PAU. The research findings will be shared with the scientific community, aiding future research.
Additionally, the study explored using “polygenic risk scores” (PRS) to estimate an individual’s genetic risk for PAU.
While not yet ready for clinical application, the PRS for PAU was tested for association with hundreds of medical traits in multiple biobanks, revealing genetic correlations between PAU and various mental and neurological disorders.
This study marks a significant step forward in the field of addiction research, offering new avenues for treatment and a better understanding of the genetic underpinnings of problematic alcohol use.
If you care about alcohol, please read studies about Why drinking less alcohol can make your brain healthier and findings of Many cancer survivors drink alcohol too much.
For more information about alcohol, please see recent studies about moderate alcohol drinking linked to high blood pressure, and results showing this drug combo shows promise for treating alcoholism.
The research findings can be found in Nature Medicine.
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