Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits.
| 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. |
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| Authors: | Johnson EC; Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.; Lai D; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.; Balbona JV; Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.; Miller AP; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.; Hatoum AS; Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.; Deak JD; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.; Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.; Jennings M; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Baranger DAA; Department of Psychological and Brain Sciences, Washington University in St Louis, Saint Louis, MO, USA.; Galimberti M; Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.; Department of Human Genetics, Yale University School of Medicine, New Haven, CT, USA.; Sanichwankul K; Suanprung Psychiatric Hospital, Chiang Mai, Thailand.; Thorgeirsson T; deCODE Genetics/Amgen, Sturlugata 8, IS-101, Reykjavik, Iceland.; Colbert SMC; Department of Genetics and Genomic Sciences, https://ror.org/04a9tmd77Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Adhikari K; Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.; Department of Human Genetics, Yale University School of Medicine, New Haven, CT, USA.; Docherty AR; Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA.; Degenhardt L; National Drug and Alcohol Research Centre, https://ror.org/03r8z3t63University of New South Wales, Sydney, Australia.; Edwards T; Department of Psychology, https://ror.org/017zqws13University of Minnesota Twin Cities, Minneapolis, MN, USA.; Fox L; Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.; Giannelis A; Department of Psychology, https://ror.org/017zqws13University of Minnesota Twin Cities, Minneapolis, MN, USA.; Jeffries PW; Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.; Korhonen T; Institute for Molecular Medicine Finland, https://ror.org/040af2s02University of Helsinki, Helsinki, Finland.; Morrison CL; Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.; Nunez YZ; Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.; Department of Human Genetics, Yale University School of Medicine, New Haven, CT, USA.; Palviainen T; Institute for Molecular Medicine Finland, https://ror.org/040af2s02University of Helsinki, Helsinki, Finland.; Su MH; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.; Romero Villela PN; Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.; Wetherill L; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.; Willoughby EA; Department of Psychology, https://ror.org/017zqws13University of Minnesota Twin Cities, Minneapolis, MN, USA.; Zellers SM; Institute for Molecular Medicine Finland, https://ror.org/040af2s02University of Helsinki, Helsinki, Finland.; Bierut LJ; Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.; Buchwald J; Institute for Molecular Medicine Finland, https://ror.org/040af2s02University of Helsinki, Helsinki, Finland.; Copeland WE; Department of Psychiatry, College of Medicine, University of Vermont, Burlington, VT, USA.; Corley RP; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.; Friedman NP; Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.; Foroud TM; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.; Gillespie NA; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; Gizer IR; Department of Psychological Sciences, https://ror.org/02ymw8z06University of Missouri, Columbia, MO, USA.; Heath AC; Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.; Hickie IB; Brain and Mind Institute, https://ror.org/0384j8v12University of Sydney, Sydney, NSW, Australia.; Kaprio J; Institute for Molecular Medicine Finland, https://ror.org/040af2s02University of Helsinki, Helsinki, Finland.; Keller MC; Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.; Lee JJ; Department of Psychology, https://ror.org/017zqws13University of Minnesota Twin Cities, Minneapolis, MN, USA.; Lind P; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.; School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.; Madden PA; Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.; Maes HHM; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.; Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA.; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.; Martin NG; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; McGue M; Department of Psychology, https://ror.org/017zqws13University of Minnesota Twin Cities, Minneapolis, MN, USA.; Medland SE; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; School of Psychology and Counselling, Queensland University of Technology, Brisbane, Australia.; School of Psychology, University of Queensland, Brisbane, Australia.; Nelson EC; Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA.; Pearson J; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; Faculty of Medicine, The University of Queensland, Brisbane, Australia.; Porjesz B; Henri Begleiter Neurodynamics Laboratory, Department of Psychiatry, SUNY Downstate Health Science University, Brooklyn, NY, USA.; Stallings MC; Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.; Vrieze S; Department of Psychology, https://ror.org/017zqws13University of Minnesota Twin Cities, Minneapolis, MN, USA.; Wilhelmson KC; Department of Neurology and Genetics and the Bowles Center of Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA.; Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA.; Renaissance Computing Institute, Chapel Hill, NC, USA.; Kranzler HR; Mental Illness Research, Education and Clinical Center, Crescenz VAMC, Philadelphia, PA, USA.; Center for Studies of Addiction, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Walters RK; Analytic and Translational Genetics Unit, https://ror.org/002pd6e78Massachusetts General Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Polimanti R; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.; Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), VA Connecticut Healthcare System, West Haven, CT, USA.; Wu Tsai Institute, Yale University, New Haven, CT, USA.; Malison R; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.; The Clinical Neuroscience Research Unit, Connecticut Mental Health Center, New Haven, CT, USA.; Zhou H; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.; Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.; Stefansson K; deCODE Genetics/Amgen, Sturlugata 8, IS-101, Reykjavik, Iceland.; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.; Sanchez-Roige S; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.; Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Potenza M; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.; Wu Tsai Institute, Yale University, New Haven, CT, USA.; Child Study Center, Yale School of Medicine, New Haven, CT, USA.; Connecticut Council on Problem Gambling, Wethersfield, CT, USA.; Connecticut Mental Health Center, New Haven, CT, USA.; Mutirangura A; Department of Anatomy, Faculty of Medicine, https://ror.org/028wp3y58Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.; Shotelersuk V; Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, https://ror.org/028wp3y58Chulalongkorn University, Bangkok, Thailand.; Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand.; Kalayasiri R; Department of Psychiatry, Epidemiology of Psychiatric Disorders and Mental Health Research Unit, Faculty of Medicine, https://ror.org/028wp3y58Chulalongkorn University, Bangkok, Thailand.; Department of Psychiatry, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.; Edenberg HJ; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.; Gelernter J; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.; Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.; Department of Human Genetics, Yale University School of Medicine, New Haven, CT, USA.; Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.; Agrawal A; Department of Psychiatry, Washington University School of Medicine in St Louis, Saint Louis, MO, USA. |
| Source: | Psychological medicine [Psychol Med] 2025 Aug 20; Vol. 55, pp. e234. Date of Electronic Publication: 2025 Aug 20. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Cambridge University Press Country of Publication: England NLM ID: 1254142 Publication Model: Electronic Cited Medium: Internet ISSN: 1469-8978 (Electronic) Linking ISSN: 00332917 NLM ISO Abbreviation: Psychol Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: London : Cambridge University Press; Original Publication: London, British Medical Assn. |
| MeSH Terms: | Tobacco Use Disorder*/genetics ; Tobacco Use Disorder*/ethnology ; Substance-Related Disorders*/genetics; Receptors, Nicotinic/genetics ; White People/genetics ; Asian People/genetics ; Black People/genetics ; Nerve Tissue Proteins/genetics ; Alcoholism/genetics ; Humans ; Genome-Wide Association Study ; Male ; Female ; Adult ; Polymorphism, Single Nucleotide ; Middle Aged ; Diagnostic and Statistical Manual of Mental Disorders ; Phenotype |
| Abstract: | Background: Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.; Methods: 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: We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E-11 in EUR; 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 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: 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. |
| Comments: | Update of: medRxiv. 2025 Feb 03:2025.01.29.25320962. doi: 10.1101/2025.01.29.25320962.. (PMID: 39974067) |
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| Grant Information: | RC2 DA028909 United States DA NIDA NIH HHS; K24 DA032555 United States DA NIDA NIH HHS; N01 HG065403 United States HG NHGRI NIH HHS; R01 MH077874 United States MH NIMH NIH HHS; R01 AA009203 United States AA NIAAA NIH HHS; U01 HG004422 United States HG NHGRI NIH HHS; R01 MH048085 United States MH NIMH NIH HHS; R01 MH063671 United States MH NIMH NIH HHS; R01 AA007535 United States AA NIAAA NIH HHS; K23 MH080230 United States MH NIMH NIH HHS; R01 DA035804 United States DA NIDA NIH HHS; U01 HG004438 United States HG NHGRI NIH HHS; R01 AA014041 United States AA NIAAA NIH HHS; K05 AA017688 United States AA NIAAA NIH HHS; U01 HG004446 United States HG NHGRI NIH HHS; R01 DA012690 United States DA NIDA NIH HHS; R01 DA012849 United States DA NIDA NIH HHS; P50 AA011998 United States AA NIAAA NIH HHS; R01 MH063970 United States MH NIMH NIH HHS; R01 AA007728 United States AA NIAAA NIH HHS; R01 DA024413 United States DA NIDA NIH HHS; R01 DA021905 United States DA NIDA NIH HHS; R01 DA021913 United States DA NIDA NIH HHS; K01 AA031724 United States AA NIAAA NIH HHS; R01 AA017444 United States AA NIAAA NIH HHS; P01 CA089392 United States CA NCI NIH HHS; U01 DA024413 United States DA NIDA NIH HHS; R56 DA012854 United States DA NIDA NIH HHS; R90 NR021799 United States NR NINR NIH HHS; R01 AA013321 United States AA NIAAA NIH HHS; R01 DA018432 United States DA NIDA NIH HHS; R01 MH130448 United States MH NIMH NIH HHS; HHSN268200782096C United States HG NHGRI NIH HHS; K01 DA051759 United States DA NIDA NIH HHS; R01 DA019963 United States DA NIDA NIH HHS; R01 DA013423 United States DA NIDA NIH HHS; K02 AA018755 United States AA NIAAA NIH HHS; R01 DA012845 United States DA NIDA NIH HHS; R01 AA011330 United States AA NIAAA NIH HHS; R01 DA012854 United States DA NIDA NIH HHS; K05 AA000145 United States AA NIAAA NIH HHS; R00 DA023549 United States DA NIDA NIH HHS; K08 DA019951 United States DA NIDA NIH HHS; R01 AA017535 United States AA NIAAA NIH HHS; K01 MH093731 United States MH NIMH NIH HHS; R01 AA012502 United States AA NIAAA NIH HHS; R01 DA017305 United States DA NIDA NIH HHS; K01DA051759 United States DA NIDA NIH HHS; United Kingdom WT_ Wellcome Trust; R01 DA011301 United States DA NIDA NIH HHS; R01 AA015416 United States AA NIAAA NIH HHS; U10 AA008401 United States AA NIAAA NIH HHS; R37 AA007728 United States AA NIAAA NIH HHS; R01 AA031176 United States AA NIAAA NIH HHS; R01 AA013320 United States AA NIAAA NIH HHS; P60 DA011015 United States DA NIDA NIH HHS; R37 AA012502 United States AA NIAAA NIH HHS |
| Contributed Indexing: | Keywords: addiction; genome-wide association study; nicotine dependence; polygenic risk; psychiatric disorders |
| Substance Nomenclature: | 0 (Receptors, Nicotinic); 0 (CHRNA5 protein, human); 0 (Nerve Tissue Proteins) |
| Entry Date(s): | Date Created: 20250820 Date Completed: 20250820 Latest Revision: 20260514 |
| Update Code: | 20260514 |
| PubMed Central ID: | PMC12360691 |
| DOI: | 10.1017/S0033291725100883 |
| PMID: | 40831304 |
| Database: | MEDLINE |
Journal Article