Functional validity, role, and implications of heavy alcohol consumption genetic loci

Thompson, Andrew ORCID: 0000-0002-7087-9415, Cook, James, Choquet, Hélène, Jorgenson, Eric, Yin, Jie, Kinnunen, Tarja, Barclay, Jeff, Morris, Andrew P and Pirmohamed, Munir ORCID: 0000-0002-7534-7266
(2020) Functional validity, role, and implications of heavy alcohol consumption genetic loci. Science Advances, 6 (3). eaay5034-eaay5034.

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<jats:p>High alcohol consumption is a risk factor for morbidity and mortality, yet few genetic loci have been robustly associated with alcohol intake. Here, we use U.K. Biobank (<jats:italic>n</jats:italic> = 125,249) and GERA (<jats:italic>n</jats:italic> = 47,967) datasets to determine genetic factors associated with extreme population-level alcohol consumption and examine the functional validity of outcomes using model organisms and in silico techniques. We identified six loci attaining genome-wide significant association with alcohol consumption after meta-analysis and meeting our criteria for replication: <jats:italic>ADH1B</jats:italic> (lead SNP: rs1229984), <jats:italic>KLB</jats:italic> (rs13130794), <jats:italic>BTF3P13</jats:italic> (rs144198753), <jats:italic>GCKR</jats:italic> (rs1260326), <jats:italic>SLC39A8</jats:italic> (rs13107325), and <jats:italic>DRD2</jats:italic> (rs11214609). A conserved role in phenotypic responses to alcohol was observed for all genetic targets available for investigation (<jats:italic>ADH1B, GCKR, SLC39A8</jats:italic>, and <jats:italic>KLB</jats:italic>) in <jats:italic>Caenorhabditis elegans</jats:italic>. Evidence of causal links to lung cancer, and shared genetic architecture with gout and hypertension was also found. These findings offer insight into genes, pathways, and relationships for disease risk associated with high alcohol consumption.</jats:p>

Item Type: Article
Uncontrolled Keywords: Humans, Alcoholism, Genetic Predisposition to Disease, Alcohol Dehydrogenase, Alcohol Drinking, Signal Transduction, Linkage Disequilibrium, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Female, Male, Genome-Wide Association Study, Genetic Loci, Genetic Association Studies, Biomarkers
Depositing User: Symplectic Admin
Date Deposited: 28 Jan 2020 11:24
Last Modified: 19 Jan 2023 00:06
DOI: 10.1126/sciadv.aay5034
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