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Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits

Open access
Zhou, Hang, Sealock, Julia M., Sanchez-Roige, Sandra, Clarke, Toni-Kim, Levey, Daniel F., Cheng, Zhongshan, Li, Boyang, Polimanti, Renato, Kember, Rachel L., Smith, Rachel Vickers, Thygesen, Johan H., Morgan, Marsha Y., Atkinson, Stephen R., Thursz, Mark R., Nyegaard, Mette, Mattheisen, Manuel, Børglum, Anders D., Johnson, Emma C., Justice, Amy C., Palmer, Abraham A., McQuillin, Andrew, Davis, Lea K., Edenberg, Howard J., Agrawal, Arpana, Kranzler, Henry R., Gelernter, Joel·2020·Nature Neuroscience

Abstract

Abstract Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. Although genome-wide association studies (GWASs) 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 genomic conserved and regulatory 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 outcomes.

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Metadata

Authors
Zhou, H., Sealock, J. M., Sanchez-Roige, S., Clarke, T.-K., Levey, D. F., Cheng, Z., Li, B., Polimanti, R., Kember, R. L., Smith, R. V., Thygesen, J. H., Morgan, M. Y., Atkinson, S. R., Thursz, M. R., Nyegaard, M., Mattheisen, M., Børglum, A. D., Johnson, E. C., Justice, A. C., Palmer, A. A., McQuillin, A., Davis, L. K., Edenberg, H. J., Agrawal, A., Kranzler, H. R., & Gelernter, J.
Venue
Nature Neuroscience
Published
2020-05-25
Volume
23
Issue
7
Pages
809-818
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W3026319555
Cited by
359
References
70
FWCI
7.76
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. https://app.cochat.ai/papers/10.1038/s41593-020-0643-5
The paper
Zhou, H., Sealock, J. M., Sanchez-Roige, S., Clarke, T.-K., Levey, D. F., Cheng, Z., Li, B., Polimanti, R., Kember, R. L., Smith, R. V., Thygesen, J. H., Morgan, M. Y., Atkinson, S. R., Thursz, M. R., Nyegaard, M., Mattheisen, M., Børglum, A. D., Johnson, E. C., Justice, A. C., . . . Gelernter, J. (2020). Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. Nature Neuroscience. https://doi.org/10.1038/s41593-020-0643-5

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.