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Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes.
Toikumo, Sylvanus; Jennings, Mariela V; Pham, Benjamin K; Lee, Hyunjoon; Mallard, Travis T; Bianchi, Sevim B; Meredith, John J; Vilar-Ribó, Laura; Xu, Heng; Hatoum, Alexander S; Johnson, Emma C; Pazdernik, Vanessa K; 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.
Affiliation
  • Toikumo S; Mental Illness Research, Education and Clinical Center, Crescenz VAMC, Philadelphia, PA, USA.
  • Jennings MV; Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Pham BK; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
  • Lee H; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
  • Mallard TT; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Bianchi SB; Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Meredith JJ; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
  • Vilar-Ribó L; Center for Precision Psychiatry, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
  • Xu H; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Boston, MA, USA.
  • Hatoum AS; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
  • Johnson EC; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
  • Pazdernik VK; Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
  • Jinwala Z; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
  • Pakala SR; Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, USA.
  • Leger BS; Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, USA.
  • Niarchou M; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
  • Ehinmowo M; Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Jenkins GD; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
  • Batzler A; Program in Biomedical Sciences, University of California San Diego, La Jolla, CA, USA.
  • Pendegraft R; Department of Medicine, Division of Genetic Medicine, Vanderbilt University, Nashville, TN, USA.
  • Palmer AA; Department of Psychology, University of Ibadan, Ibadan, Nigeria.
  • Biernacka JM; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
  • Coombes BJ; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
  • Gelernter J; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
  • Xu K; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
  • Hancock DB; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
  • Cox NJ; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
  • Smoller JW; Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.
  • Davis LK; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
  • Justice AC; Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
  • Kranzler HR; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
  • Kember RL; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
  • Sanchez-Roige S; Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.
Nat Hum Behav ; 8(6): 1177-1193, 2024 Jun.
Article in En | MEDLINE | ID: mdl-38632388
ABSTRACT
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 (ncombined = 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.
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Full text: 1 Database: MEDLINE Main subject: Tobacco Use Disorder Limits: Female / Humans / Male Country/Region as subject: America do norte Language: En Year: 2024 Type: Article
Fulltext
Print
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PubMed Links
Search on Google

Full text: 1 Database: MEDLINE Main subject: Tobacco Use Disorder Limits: Female / Humans / Male Country/Region as subject: America do norte Language: En Year: 2024 Type: Article