Pulse Brain · Growing Health Evidence Index
Peer-reviewed

Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals

Hang Zhou, Rachel L. Kember, Joseph D. Deak, Heng Xu, Sylvanus Toikumo, Kai Yuan, Penelope A. Lind, Leila Farajzadeh, Lu Wang, Alexander S. Hatoum, Jessica Johnson, Hyunjoon Lee, Travis T. Mallard, Jiayi Xu, Keira J.A. Johnston, Emma C. Johnson, Trine Tollerup Nielsen, Marco Galimberti, Cecilia Dao, Daniel F. Levey, Cassie Overstreet, Enda M. Byrne, Nathan A. Gillespie, Scott D. Gordon, Ian B. Hickie, John B. Whitfield, Ke Xu, Hongyu Zhao, Laura M. Huckins, Lea K. Davis, Sandra Sanchez‐Roige, Pamela A. F. Madden, Andrew C. Heath, Sarah E. Medland, Nicholas G. Martin, Tian Ge, Jordan W. Smoller, David M. Hougaard, Anders D. Børglum, Ditte Demontis, John H. Krystal, J. Michael Gaziano, Howard J. Edenberg, Arpana Agrawal, Million Veteran Program, Hongyu Zhao, Amy C. Justice, Murray B. Stein, Henry R. Kranzler, Joel Gelernter

Nature Medicine · 2023

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Summary

Problematic alcohol use (PAU), a trait that combines alcohol use disorder and alcohol-related problems assessed with a questionnaire, is a leading cause of death and morbidity worldwide. Here we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals (European, N = 903,147; African, N = 122,571; Latin American, N = 38,962; East Asian, N = 13,551; and South Asian, N = 1,716 ancestries). We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine mapping improved the identification of likely causal variants. Prioritizing genes through gene expression and chromatin interaction in brain tissues identified multiple genes associated with P

Source type
Peer-reviewed study
DOI
10.1038/s41591-023-02653-5
Catalogue ID
SNmojad6s2-kvrcbh
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