In a groundbreaking study published in Nature Medicine, researchers from VA Connecticut Healthcare Center and Yale University shed light on the shared genetic architecture underlying problematic alcohol use (PAU) across various ancestries worldwide. The study, the largest of its kind to date, not only identifies new risk genes but also unveils significant insights into the biology of PAU, paving the way for potential treatments.
Led by Dr. Hang Zhou, Assistant Professor of Psychiatry and Biomedical Informatics & Data Science at Yale School of Medicine, the research focused on over 1 million individuals with PAU, encompassing diverse genetic ancestral groups, including European, African, Latin American, East Asian, and South Asian ancestries. Leveraging data from the Million Veteran Program (MVP) and other sources, the study demonstrates that while there are genetic differences in PAU among populations, there is a substantial shared genetic architecture across diverse groups.
Dr. Zhou emphasized the importance of understanding the molecular mechanisms of PAU, stating, "Research focused on understanding the molecular mechanism underlying PAU and identification of gene targets for potential pharmacological studies is extremely important for future treatments and could help mitigate the consequences of excessive alcohol use."
The study identified 110 gene regions by leveraging multi-ancestry information, providing a more nuanced understanding of the potential causal variants in each region. Various methods, including gene expression and chromatin interaction analyses in the brain, were employed to prioritize genes associated with PAU. These findings offer valuable resources and targets for future functional analyses and drug development.
Senior author Dr. Joel Gelernter, Foundations Fund Professor of Psychiatry at Yale School of Medicine, highlighted the significance of the research, stating, "The resulting data allowed us to understand the biology of PAU better, suggesting some already-approved drugs that might become tools for treating PAU in the future, with additional research."
Additionally, the study conducted drug-repurposing analyses, identifying existing medications with the potential to serve as treatments for PAU. The genome-wide association data generated by the study can be used to compute polygenic risk scores (PRS) for estimating an individual's genetic risk for PAU. While the PRS is not yet ready for clinical use, the researchers tested its association with various medical traits, revealing genetic correlations between PAU and numerous mental and neurological disorders.
The research team emphasizes the importance of sharing their data with the scientific community to advance future research in understanding and addressing problematic alcohol use.
More: https://medicalxpress.com/news/2023-12-multi-ancestry-uncovers-genetics-problematic.html
