| Title: | Functional validity, role, and implications of heavy alcohol consumption genetic loci |
| Journal: | Science Advances |
| Published: | 15 Jan 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/31998841/ |
| DOI: | https://doi.org/10.1126/sciadv.aay5034 |
| URL: | https://advances.sciencemag.org/content/advances/6/3/eaay5034.full.pdf |
| Citations: | 50 (16 in last 2 years) as of 8 Aug 2024 |
Publication 4872
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
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 (n = 125,249) and GERA (n = 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: ADH1B (lead SNP: rs1229984), KLB (rs13130794), BTF3P13 (rs144198753), GCKR (rs1260326), SLC39A8 (rs13107325), and DRD2 (rs11214609). A conserved role in phenotypic responses to alcohol was observed for all genetic targets available for investigation (ADH1B, GCKR, SLC39A8, and KLB) in Caenorhabditis elegans. 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.</p>
16 Keywords
- Alcohol Dehydrogenase
- Alcohol Drinking
- Alcoholism
- Biomarkers
- Female
- Genetic Association Studies
- Genetic Loci
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Linkage Disequilibrium
- Male
- Phenotype
- Polymorphism, Single Nucleotide
- Quantitative Trait Loci
- Signal Transduction
9 Authors
- Andrew Thompson
- James Cook
- Hélène Choquet
- Eric Jorgenson
- Jie Yin
- Tarja Kinnunen
- Jeff Barclay
- Andrew P. Morris
- Munir Pirmohamed
Enabling scientific discoveries that improve human health