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
40831304
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
BACKGROUND NlmCategory: BACKGROUND
Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.
METHODS NlmCategory: METHODS
Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement. We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.
RESULTS NlmCategory: RESULTS
Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement. We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 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 single-nucleotide polymorphism [SNP]: rs147144681,  = 1.27E-11 in EUR; lead SNP = rs2036527,  = 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 criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a "problematic tobacco use" factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).
CONCLUSIONS NlmCategory: CONCLUSIONS
Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement. We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 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 single-nucleotide polymorphism [SNP]: rs147144681,  = 1.27E-11 in EUR; lead SNP = rs2036527,  = 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 criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a "problematic tobacco use" factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs). Our results suggest 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 Aug 20
HISTORY
PUBSTATUS PUBSTATUSDATE
medline 2025/08/20 06:30
pubmed 2025/08/20 06:29
entrez 2025/08/20 03:34
pmc-release 2025/08/18
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.
Balbona JV Balbona Jared V JV Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, 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.
Jennings M Jennings Mariela M Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Baranger DAA Baranger David A A DAA Department of Psychological and Brain Sciences, Washington University in St Louis, Saint Louis, MO, USA.
Galimberti M Galimberti Marco M Department of Human Genetics, Yale University School of Medicine, New 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 SMC Colbert Sarah M C SMC Department of Genetics and Genomic Sciences, https://ror.org/04a9tmd77Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Adhikari K Adhikari Keyrun K Department of Human Genetics, Yale University School of Medicine, New Haven, CT, USA.
Docherty AR Docherty Anna R AR 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, https://ror.org/03r8z3t63University of New South Wales, Sydney, Australia.
Edwards T Edwards Tobias T Department of Psychology, https://ror.org/017zqws13University 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, https://ror.org/017zqws13University of Minnesota Twin Cities, Minneapolis, MN, USA.
Jeffries PW Jeffries Paul W PW 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, https://ror.org/040af2s02University of Helsinki, Helsinki, Finland.
Morrison CL Morrison Claire L CL Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Nunez YZ Nunez Yaira Z YZ Department of Human Genetics, Yale University School of Medicine, New Haven, CT, USA.
Palviainen T Palviainen Teemu T Institute for Molecular Medicine Finland, https://ror.org/040af2s02University of Helsinki, Helsinki, Finland.
Su MH Su Mei-Hsin MH Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Romero Villela PN Romero Villela Pamela N PN 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, https://ror.org/017zqws13University of Minnesota Twin Cities, Minneapolis, MN, USA.
Zellers SM Zellers Stephanie M SM Institute for Molecular Medicine Finland, https://ror.org/040af2s02University of Helsinki, Helsinki, Finland.
Bierut LJ Bierut Laura J LJ 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, https://ror.org/040af2s02University of Helsinki, Helsinki, Finland.
Copeland WE Copeland William E WE Department of Psychiatry, College of Medicine, University of Vermont, Burlington, VT, USA.
Corley RP Corley Robin P RP 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, https://ror.org/02ymw8z06University 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, https://ror.org/0384j8v12University of Sydney, Sydney, NSW, Australia.
Kaprio J Kaprio Jaakko J Institute for Molecular Medicine Finland, https://ror.org/040af2s02University of Helsinki, Helsinki, Finland.
Keller MC Keller Matthew C MC Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Lee JJ Lee James J JJ Department of Psychology, https://ror.org/017zqws13University of Minnesota Twin Cities, Minneapolis, MN, USA.
Lind P Lind Penelope P 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 HHM Maes Hermine H M HHM 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, https://ror.org/017zqws13University 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 J Pearson John J 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 MC Stallings Michael C MC Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Vrieze S Vrieze Scott S Department of Psychology, https://ror.org/017zqws13University of Minnesota Twin Cities, Minneapolis, MN, USA.
Wilhelmson KC Wilhelmson Kirk C KC Renaissance Computing Institute, Chapel Hill, NC, USA.
Kranzler HR Kranzler Henry R HR Center for Studies of Addiction, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 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 R Malison Robert R 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, Reykjavik, Iceland.
Sanchez-Roige S Sanchez-Roige Sandra S Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Potenza M Potenza Marc M Connecticut Mental Health Center, New Haven, CT, USA.
Mutirangura A Mutirangura Apiwat A Department of Anatomy, Faculty of Medicine, https://ror.org/028wp3y58Chulalongkorn 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: 55
ISSUE:
TITLE: Psychological medicine
ISOABBREVIATION: Psychol Med
YEAR: 2025
MONTH: Aug
DAY: 20
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1469-8978
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Psychol Med
COUNTRY: England
ISSNLINKING: 0033-2917
NLMUNIQUEID: 1254142
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
UpdateOf medRxiv. 2025 Feb 03:2025.01.29.25320962. doi: 10.1101/2025.01.29.25320962. 39974067
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Wellcome Trust United Kingdom
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GENERAL NOTE
KEYWORDS
KEYWORD
addiction
genome-wide association study
nicotine dependence
polygenic risk
psychiatric disorders
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Humans
Genome-Wide Association Study
Tobacco Use Disorder ethnology
Male ethnology
Female ethnology
Adult ethnology
Polymorphism, Single Nucleotide ethnology
Middle Aged ethnology
Receptors, Nicotinic genetics
Substance-Related Disorders genetics
White People genetics
Asian People genetics
Black People genetics
Diagnostic and Statistical Manual of Mental Disorders genetics
Nerve Tissue Proteins genetics
Phenotype genetics
Alcoholism genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Receptors, Nicotinic
0 CHRNA5 protein, human
0 Nerve Tissue Proteins
OTHER ID's
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