Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes.
Journal: Nature human behaviour
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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, La Jolla, CA, USA.
Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, 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.
Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, USA.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Medicine, Division of Genetic Medicine, Vanderbilt University, Nashville, TN, USA.
Department of Psychology, University of Ibadan, Ibadan, Nigeria.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
RTI International, Research Triangle Park, NC, USA.
Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA. sanchezroige@ucsd.edu.
Abstract summary
Tobacco use disorder (TUD) is the most prevalent substance use disorder in the world. Genetic factors influence smoking behaviours and although strides have been made using genome-wide association studies to identify risk variants, most variants identified have been for nicotine consumption, rather than TUD. Here we leveraged four US biobanks to perform a multi-ancestral meta-analysis of TUD (derived via electronic health records) in 653,790 individuals (495,005 European, 114,420 African American and 44,365 Latin American) and data from UK Biobank (n = 898,680). 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 behaviours in children and hundreds of medical outcomes, including HIV infection, heart disease and pain. This work furthers our biological understanding of TUD and establishes electronic health records 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 K VK
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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