Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
39974067
TITLE
Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits.
ABSTRACT
Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement. We conducted a genome-wide association study of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry, 10,231 of African ancestry, 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes. We replicated the well-known association at the locus (lead SNP: rs147144681, p =1.27E-11 in European ancestry; lead SNP = rs2036527, p = 6.49e-13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder and 6 of 11 individual diagnostic criteria, but none of the Fagerström Test for Nicotine Dependence (FTND) items, in the independent NESARC-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than did a "problematic tobacco use" factor (a combination of cigarettes per day and nicotine dependence defined by the FTND). Finally, DSM-NicDep was strongly genetically correlated with a GWAS of tobacco use disorder as defined in electronic health records, suggesting that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.
DATE PUBLISHED
2025 Feb 03
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2025/02/20 06:22
medline 2025/02/20 06:23
entrez 2025/02/20 05:25
pmc-release 2025/02/19
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Johnson EC Johnson Emma C EC Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.
Lai D Lai Dongbing D Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Miller AP Miller Alex P AP Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
Hatoum AS Hatoum Alexander S AS Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.
Deak JD Deak Joseph D JD Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.
Balbona JV Balbona Jared V JV Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.
Baranger DA Baranger David Aa DA Department of Psychological and Brain Sciences, Washington University in St Louis, Saint Louis, MO, USA.
Galimberti M Galimberti Marco M Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.
Sanichwankul K Sanichwankul Kittipong K Suanprung Psychiatric Hospital, Chiang Mai, Thailand.
Thorgeirsson T Thorgeirsson Thorgeir T deCODE Genetics/Amgen, Sturlugata 8, IS-101, Reykjavik, Iceland.
Colbert SM Colbert Sarah Mc SM Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Sanchez-Roige S Sanchez-Roige Sandra S Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Adhikari K Adhikari Keyrun K Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.
Docherty A Docherty Anna A Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA.
Degenhardt L Degenhardt Louisa L National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.
Edwards T Edwards Tobias T Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Fox L Fox Louis L Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.
Giannelis A Giannelis Alexandros A Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Jeffries P Jeffries Paul P Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.
Korhonen T Korhonen Tellervo T Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Morrison C Morrison Claire C Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Nunez YZ Nunez Yaira Z YZ Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.
Palviainen T Palviainen Teemu T Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Su MH Su Mei-Hsin MH Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Villela PNR Villela Pamela N Romero PNR Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Wetherill L Wetherill Leah L Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Willoughby EA Willoughby Emily A EA Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Zellers S Zellers Stephanie S Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Bierut L Bierut Laura L Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.
Buchwald J Buchwald Jadwiga J Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Copeland W Copeland William W Department of Psychiatry, College of Medicine, University of Vermont, Burlington, VT, USA.
Corley R Corley Robin R Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Friedman NP Friedman Naomi P NP Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Foroud TM Foroud Tatiana M TM Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Gillespie NA Gillespie Nathan A NA QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Gizer IR Gizer Ian R IR Department of Psychological Sciences, University of Missouri, Columbia, MO, USA.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.
Hickie IB Hickie Ian B IB Brain and Mind Institute, University of Sydney, New South Wales, Sydney, Australia.
Kaprio JA Kaprio Jaakko A JA Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Keller MC Keller Matthew C MC Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Lee JL Lee James L JL Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Lind PA Lind Penelope A PA School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
Madden PA Madden Pamela A PA Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.
Maes HH Maes Hermine Hm HH Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
McGue M McGue Matt M Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Medland SE Medland Sarah E SE School of Psychology, University of Queensland, Brisbane, Australia.
Nelson EC Nelson Elliot C EC Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.
Pearson JV Pearson John V JV Faculty of Medicine, The University of Queensland, Brisbane, Australia.
Porjesz B Porjesz Bernice B Henri Begleiter Neurodynamics Laboratory, Department of Psychiatry, SUNY Downstate Health Science University, Brooklyn, NY, USA.
Stallings M Stallings Michael M Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Vrieze S Vrieze Scott S Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Wilhelmsen KC Wilhelmsen Kirk C KC Renaissance Computing Institute, Chapel Hill, NC, USA.
Walters RK Walters Raymond K RK Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Polimanti R Polimanti Renato R Wu Tsai Institute, Yale University, New Haven, CT, USA.
Malison RT Malison Robert T RT The Clinical Neuroscience Research Unit, Connecticut Mental Health Center, New Haven, CT, USA.
Zhou H Zhou Hang H Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.
Stefansson K Stefansson Kari K Faculty of Medicine, University of Iceland, IS-101, Reykjavik, Iceland.
Potenza MN Potenza Marc N MN Connecticut Mental Health Center, New Haven, CT, USA.
Mutirangura A Mutirangura Apiwat A Department of Anatomy, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Shotelersuk V Shotelersuk Vorasuk V Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand.
Kalayasiri R Kalayasiri Rasmon R Department of Psychiatry, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Edenberg HJ Edenberg Howard J HJ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Gelernter J Gelernter Joel J Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
Agrawal A Agrawal Arpana A Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: medRxiv : the preprint server for health sciences
ISOABBREVIATION: medRxiv
YEAR: 2025
MONTH: Feb
DAY: 03
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN:
ISSNTYPE:
MEDLINE JOURNAL
MEDLINETA: medRxiv
COUNTRY: United States
ISSNLINKING:
NLMUNIQUEID: 101767986
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Preprint
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