Multi-ancestry meta-analysis of tobacco use disorder prioritizes novel candidate risk genes and reveals associations with numerous health outcomes
Toikumo, Sylvanus (University of Pennsylvania Perelman School of Medicine)
Jennings, Mariela V (University of California San Diego)
Pham, Benjamin K (University of California San Diego)
Lee, Hyunjoon (Massachusetts General Hospital (Boston))
Mallard, Travis T (Harvard Medical School)
Bianchi, Sevim B (University of California San Diego)
Meredith, John J (University of California San Diego)
Vilar-Ribó, L (Hospital Universitari Vall d'Hebron)
Xu, Heng (University of California San Diego)
Hatoum, Alexander S (Washington University School of Medicine)
Johnson, Emma C (Washington University School of Medicine)
Pazdernik, Vanessa (Mayo Clinic)
Jinwala, Zeal (University of Pennsylvania Perelman School of Medicine)
Pakala, Shreya R (University of California San Diego)
Leger, Brittany S (University of California San Diego)
Niarchou, Maria (Vanderbilt Genetics Institute)
Ehinmowo, Michael (University of Ibadan)
Jenkins, Greg D (Mayo Clinic)
Batzler, Anthony (Mayo Clinic)
Pendegraft, Richard (Mayo Clinic)
Palmer, Abraham A (University of California San Diego)
Zhou, Hang (Veterans Affairs Connecticut Healthcare System)
Biernacka, Joanna M (Mayo Clinic)
Coombes, Brandon J (Mayo Clinic)
Gelernter, Joel (Veterans Affairs Connecticut Healthcare System)
Xu, Ke (Veterans Affairs Connecticut Healthcare System)
Hancock, Dana B (RTI International)
Cox, Nancy J (Vanderbilt University)
Smoller, Jordan W (Harvard Medical School)
Davis, Lea K (Vanderbilt University Medical Center)
Justice, Amy C (Yale University School of Medicine)
Kranzler, Henry R (University of Pennsylvania Perelman School of Medicine)
Kember, Rachel L (University of Pennsylvania Perelman School of Medicine)
Sanchez-Roige, Sandra (Vanderbilt University)
Universitat Autònoma de Barcelona

Fecha:	2023
Resumen:	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.
Derechos:	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.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	medRxiv, september 2023

DOI: 10.1101/2023.03.27.23287713
PMID: 37034728

58 p, 884.9 KB

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