Multi-ancestry meta-analysis of tobacco use disorder prioritizes novel candidate risk genes and reveals associations with numerous health outcomes.

Autor:	Toikumo S; Mental Illness Research, Education and Clinical Center, Crescenz VAMC, Philadelphia, PA, USA.; Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Jennings MV; Department of Psychiatry, University of California San Diego, San Diego, CA, USA., Pham BK; Department of Psychiatry, University of California San Diego, San Diego, CA, USA., Lee H; Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA., Mallard TT; Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Psychiatry, Harvard Medical School, Boston, MA, USA., Bianchi SB; Department of Psychiatry, University of California San Diego, San Diego, CA, USA., Meredith JJ; Department of Psychiatry, University of California San Diego, San Diego, CA, USA., Vilar-Ribó L; Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain., Xu H; Department of Psychiatry, University of California San Diego, San Diego, CA, USA., Hatoum AS; Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, USA., Johnson EC; Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, USA., Pazdernik V; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA., Jinwala Z; Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Pakala SR; Department of Psychiatry, University of California San Diego, San Diego, CA, USA., Leger BS; Department of Psychiatry, University of California San Diego, San Diego, CA, USA.; Program in Biomedical Sciences, University of California San Diego, La Jolla, CA, USA., Niarchou M; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA., Ehinmowo M; Department of Psychology, University of Ibadan, Nigeria., Jenkins GD; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA., Batzler A; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA., Pendegraft R; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA., Palmer AA; Department of Psychiatry, University of California San Diego, San Diego, CA, USA.; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA., Zhou H; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.; Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA., Biernacka JM; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.; Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN, USA., Coombes BJ; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA., Gelernter J; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.; Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA., Xu K; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.; Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA., Hancock DB; Behavioral and Urban Health Program, Behavioral Health and Criminal Justice Division, RTI International, Research Triangle Park, NC, USA., Cox NJ; Department of Medicine, Division of Genetic Medicine, Vanderbilt University, Nashville, TN, USA., Smoller JW; Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Psychiatry, Harvard Medical School, Boston, MA, USA., Davis LK; Department of Medicine, Division of Genetic Medicine, Vanderbilt University, Nashville, TN, USA.; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA., Justice AC; Yale University School of Public Health, New Haven, CT, USA.; Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.; Yale University School of Medicine, New Haven, CT, USA., Kranzler HR; Mental Illness Research, Education and Clinical Center, Crescenz VAMC, Philadelphia, PA, USA.; Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Kember RL; Mental Illness Research, Education and Clinical Center, Crescenz VAMC, Philadelphia, PA, USA.; Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Sanchez-Roige S; Department of Psychiatry, University of California San Diego, San Diego, CA, USA.; Department of Medicine, Division of Genetic Medicine, Vanderbilt University, Nashville, TN, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2023 Sep 18. Date of Electronic Publication: 2023 Sep 18.
DOI:	10.1101/2023.03.27.23287713
Abstrakt:	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. Competing Interests: Ethics declarations Dr. Palmer is on the scientific advisory board of Vivid Genomics for which he receives stock options. Dr. Smoller is a member of the Scientific Advisory Board of Sensorium Therapeutics (with equity) and has received grant support from Biogen, Inc. He is PI of a collaborative study of the genetics of depression and bipolar disorder sponsored by 23andMe for which 23andMe provides analysis time as in-kind support but no payments. Dr. Kranzler is a member of advisory boards for Clearmind Medicine, Dicerna Pharmaceuticals, Sophrosyne Pharmaceuticals, and Enthion Pharmaceuticals; a consultant to Sobrera Pharmaceuticals; the recipient of research funding and medication supplies for an investigator-initiated study from Alkermes; a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative, which was supported in the last three years by Alkermes, Dicerna, Ethypharm, Lundbeck, Mitsubishi, Otsuka, and Pear Therapeutics; and with Dr. Gelernter, a holder of U.S. patent 10,900,082 titled: “Genotype-guided dosing of opioid agonists,” issued 26 January 2021. The other authors declare no competing interests.
Databáze:	MEDLINE
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