| Title: |
Multi-ancestry meta-analysis of tobacco use disorder prioritizes novel candidate risk genes and reveals associations with numerous health outcomes |
| Authors: |
Toikumo, Sylvanus; Jennings, Mariela V; Pham, Benjamin K; Lee, Hyunjoon; Mallard, Travis T; Bianchi, Sevim B; Meredith, John J; Vilar-Ribó, L; Xu, Heng; Hatoum, Alexander S; Johnson, Emma C; Pazdernik, Vanessa; Jinwala, Zeal; Pakala, Shreya R; Leger, Brittany S; Niarchou, Maria; Ehinmowo, Michael; Jenkins, Greg D; Batzler, Anthony; Pendegraft, Richard; Palmer, Abraham A; Zhou, Hang; Biernacka, Joanna M; Coombes, Brandon J; Gelernter, Joel; Xu, Ke; Hancock, Dana B; Cox, Nancy J; Smoller, Jordan W; Davis, Lea K; Justice, Amy C; Kranzler, Henry R; Kember, Rachel L; Sanchez-Roige, Sandra; Universitat Autònoma de Barcelona |
| Publication Year: |
2023 |
| Collection: |
Universitat Autònoma de Barcelona: Dipòsit Digital de Documents de la UAB |
| Description: |
Tobacco use disorder (TUD) is the most prevalent substance use disorder in the world. Genetic factors influence smoking behaviors, and although strides have been made using genome-wide association studies (GWAS) to identify risk variants, the majority of variants identified have been for nicotine consumption, rather than TUD. We leveraged five biobanks to perform a multi-ancestral meta-analysis of TUD (derived via electronic health records, EHR) in 898,680 individuals (739,895 European, 114,420 African American, 44,365 Latin American). We identified 88 independent risk loci; integration with functional genomic tools uncovered 461 potential risk genes, primarily expressed in the brain. TUD was genetically correlated with smoking and psychiatric traits from traditionally ascertained cohorts, externalizing behaviors in children, and hundreds of medical outcomes, including HIV infection, heart disease, and pain. This work furthers our biological understanding of TUD and establishes EHR as a source of phenotypic information for studying the genetics of TUD. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
23287713 |
| Relation: |
medRxiv; september 2023; https://ddd.uab.cat/record/283929; urn:10.1101/2023.03.27.23287713; urn:oai:ddd.uab.cat:283929; urn:pmcid:PMC10081388; urn:pmid:37034728; urn:oai:pubmedcentral.nih.gov:10081388 |
| Availability: |
https://ddd.uab.cat/record/283929 |
| 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 es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. ; https://creativecommons.org/licenses/by-nd/4.0/ |
| Accession Number: |
edsbas.A64ADC7F |
| Database: |
BASE |