Multi-ancestry meta-analysis of tobacco use disorder prioritizes novel candidate risk genes and reveals associations with numerous health outcomes.
Journal: medRxiv : the preprint server for health sciences
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Affiliated Institutions:
Mental Illness Research, Education and Clinical Center, Crescenz VAMC, Philadelphia, PA, USA.
Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, USA.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Psychology, University of Ibadan, Nigeria.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Behavioral and Urban Health Program, Behavioral Health and Criminal Justice Division, RTI International, Research Triangle Park, NC, USA.
Department of Medicine, Division of Genetic Medicine, Vanderbilt University, Nashville, TN, USA.
Yale University School of Public Health, New Haven, CT, USA.
Abstract summary
Tobacco use disorder () 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 () 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, ) 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.
Authors & Co-authors:
Toikumo Sylvanus S
Jennings Mariela V MV
Pham Benjamin K BK
Lee Hyunjoon H
Mallard Travis T TT
Bianchi Sevim B SB
Meredith John J JJ
Vilar-Ribó Laura L
Xu Heng H
Hatoum Alexander S AS
Johnson Emma C EC
Pazdernik Vanessa V
Jinwala Zeal Z
Pakala Shreya R SR
Leger Brittany S BS
Niarchou Maria M
Ehinmowo Michael M
Jenkins Greg D GD
Batzler Anthony A
Pendegraft Richard R
Palmer Abraham A AA
Zhou Hang H
Biernacka Joanna M JM
Coombes Brandon J BJ
Gelernter Joel J
Xu Ke K
Hancock Dana B DB
Cox Nancy J NJ
Smoller Jordan W JW
Davis Lea K LK
Justice Amy C AC
Kranzler Henry R HR
Kember Rachel L RL
Sanchez-Roige Sandra S
Study Outcome
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