| Title: |
A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals |
| Authors: |
Jennings, Mariela V.; Martínez-Magaña, José Jaime; Courchesne-Krak, Natasia S.; Cupertino , Renata B.; Vilar-Ribó, L.; Bianchi, Sevim B.; Hatoum, Alexander S.; Atkinson, Elizabeth G.; Giusti-Rodriguez, Paola; Montalvo-Ortiz, Janitza L.; Gelernter, Joel; Soler Artigas, María; Elson, Sarah L.; Edenberg, Howard J.; Fontanillas, Pierre; Palmer, Abraham A.; Sanchez-Roige, Sandra; Universitat Autònoma de Barcelona |
| Publication Year: |
2024 |
| Collection: |
Universitat Autònoma de Barcelona: Dipòsit Digital de Documents de la UAB |
| Subject Terms: |
Alcohol; PheWAS; Metabolising enzyme genes; ADH1B; ADH1C; Rs1229984 |
| Description: |
Alcohol consumption is associated with numerous negative social and health outcomes. These associations may be direct consequences of drinking, or they may reflect common genetic factors that influence both alcohol consumption and other outcomes. We performed exploratory phenome-wide association studies (PheWAS) of three of the best studied protective single nucleotide polymorphisms (SNPs) in genes encoding ethanol metabolising enzymes (ADH1B : rs1229984-T, rs2066702-A; ADH1C : rs698-T) using up to 1109 health outcomes across 28 phenotypic categories (e.g., substance-use, mental health, sleep, immune, cardiovascular, metabolic) from a diverse 23andMe cohort, including European (N ≤ 2,619,939), Latin American (N ≤ 446,646) and African American (N ≤ 146,776) populations to uncover new and perhaps unexpected associations. These SNPs have been consistently implicated by both candidate gene studies and genome-wide association studies of alcohol-related behaviours but have not been investigated in detail for other relevant phenotypes in a hypothesis-free approach in such a large cohort of multiple ancestries. To provide insight into potential causal effects of alcohol consumption on the outcomes significant in the PheWAS, we performed univariable two-sample and one-sample Mendelian randomisation (MR) analyses. The minor allele rs1229984-T, which is protective against alcohol behaviours, showed the highest number of PheWAS associations across the three cohorts (N = 232, European; N = 29, Latin American; N = 7, African American). rs1229984-T influenced multiple domains of health. We replicated associations with alcohol-related behaviours, mental and sleep conditions, and cardio-metabolic health. We also found associations with understudied traits related to neurological (migraines, epilepsy), immune (allergies), musculoskeletal (fibromyalgia), and reproductive health (preeclampsia). MR analyses identified evidence of causal effects of alcohol consumption on liability for 35 of these outcomes in the European cohort. Our ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
23523964 |
| Relation: |
Instituto de Salud Carlos III PI19/01224; Instituto de Salud Carlos III PI22/00464; Instituto de Salud Carlos III CP22/00128; EBioMedicine; Vol. 103 (april 2024); https://ddd.uab.cat/record/306724; urn:10.1016/j.ebiom.2024.105086; urn:oai:ddd.uab.cat:306724; urn:articleid:23523964v103a105086; urn:pmcid:PMC11121167; urn:pmid:38580523; urn:oai:pubmedcentral.nih.gov:11121167 |
| Availability: |
https://ddd.uab.cat/record/306724 |
| Rights: |
open access ; Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. ; https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.1E97E59E |
| Database: |
BASE |