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Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders.
Walters, Raymond K; Polimanti, Renato; Johnson, Emma C; McClintick, Jeanette N; Adams, Mark J; Adkins, Amy E; Aliev, Fazil; Bacanu, Silviu-Alin; Batzler, Anthony; Bertelsen, Sarah; Biernacka, Joanna M; Bigdeli, Tim B; Chen, Li-Shiun; Clarke, Toni-Kim; Chou, Yi-Ling; Degenhardt, Franziska; Docherty, Anna R; Edwards, Alexis C; Fontanillas, Pierre; Foo, Jerome C; Fox, Louis; Frank, Josef; Giegling, Ina; Gordon, Scott; Hack, Laura M; Hartmann, Annette M; Hartz, Sarah M; Heilmann-Heimbach, Stefanie; Herms, Stefan; Hodgkinson, Colin; Hoffmann, Per; Jan Hottenga, Jouke; Kennedy, Martin A; Alanne-Kinnunen, Mervi; Konte, Bettina; Lahti, Jari; Lahti-Pulkkinen, Marius; Lai, Dongbing; Ligthart, Lannie; Loukola, Anu; Maher, Brion S; Mbarek, Hamdi; McIntosh, Andrew M; McQueen, Matthew B; Meyers, Jacquelyn L; Milaneschi, Yuri; Palviainen, Teemu; Pearson, John F; Peterson, Roseann E; Ripatti, Samuli.
Affiliation
  • Walters RK; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Polimanti R; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Johnson EC; Department of Psychiatry, Yale School of Medicine and Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.
  • McClintick JN; Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA.
  • Adams MJ; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Adkins AE; University of Edinburgh, Division of Psychiatry, Edinburgh, UK.
  • Aliev F; Department of Psychology & College Behavioral and Emotional Health Institute, Virginia Commonwealth University, Richmond, VA, USA.
  • Bacanu SA; Virginia Commonwealth University, Department of Psychology, Richmond, VA, USA.
  • Batzler A; Virginia Commonwealth University Alcohol Research Center; Virginia Institute for Psychiatric and Behavioral Genetics; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
  • Bertelsen S; Mayo Clinic, Psychiatric Genomics and Pharmacogenomics Program, Rochester, MN, USA.
  • Biernacka JM; Icahn School of Medicine at Mount Sinai, Department of Neuroscience, New York, NY, USA.
  • Bigdeli TB; Mayo Clinic, Department of Health Sciences Research, and Department of Psychiatry and Psychology, Rochester, MN, USA.
  • Chen LS; Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, NY, USA.
  • Clarke TK; Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA.
  • Chou YL; University of Edinburgh, Division of Psychiatry, Edinburgh, UK.
  • Degenhardt F; Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA.
  • Docherty AR; Institute of Human Genetics, University of Bonn; and Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
  • Edwards AC; University of Utah, Department of Psychiatry, Salt Lake City, UT, USA.
  • Fontanillas P; Virginia Commonwealth University, Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Richmond, VA, USA.
  • Foo JC; 23andMe, Inc, Mountain View, CA, USA.
  • Fox L; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Frank J; Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA.
  • Giegling I; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Gordon S; Martin-Luther-University Halle-Wittenberg, Department of Psychiatry, Psychotherapy and Psychosomatics, Halle, Germany.
  • Hack LM; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Hartmann AM; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
  • Hartz SM; Martin-Luther-University Halle-Wittenberg, Department of Psychiatry, Psychotherapy and Psychosomatics, Halle, Germany.
  • Heilmann-Heimbach S; Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA.
  • Herms S; Institute of Human Genetics, University of Bonn; and Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
  • Hodgkinson C; Institute of Human Genetics, University of Bonn; and Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
  • Hoffmann P; Human Genomics Research Group, Department of Biomedicine, University of Basel Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  • Jan Hottenga J; NIH/NIAAA, Laboratory of Neurogenetics, Bethesda, MD, USA.
  • Kennedy MA; Institute of Human Genetics, University of Bonn; and Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
  • Alanne-Kinnunen M; Human Genomics Research Group, Department of Biomedicine, University of Basel Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  • Konte B; Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • Lahti J; University of Otago, Christchurch, New Zealand.
  • Lahti-Pulkkinen M; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Lai D; Martin-Luther-University Halle-Wittenberg, Department of Psychiatry, Psychotherapy and Psychosomatics, Halle, Germany.
  • Ligthart L; Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, Finland.
  • Loukola A; Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
  • Maher BS; Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
  • Mbarek H; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
  • McIntosh AM; Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • McQueen MB; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Meyers JL; Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Milaneschi Y; Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • Palviainen T; University of Edinburgh, Division of Psychiatry, Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK.
  • Pearson JF; Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
  • Peterson RE; Henri Begleiter Neurodynamics Laboratory, Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY, USA.
  • Ripatti S; Department of Psychiatry, Amsterdam Public Health Research Institute, VU University Medical Center/GGz inGeest, Amsterdam, The Netherlands.
Nat Neurosci ; 21(12): 1656-1669, 2018 12.
Article in En | MEDLINE | ID: mdl-30482948
ABSTRACT
Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10-13) and African ancestries (rs2066702; P = 2.2 × 10-9). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.
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Full text: 1 Database: MEDLINE Main subject: Genetic Predisposition to Disease / Polymorphism, Single Nucleotide / Alcoholism / Mental Disorders Type of study: Diagnostic_studies Limits: Humans Language: En Journal: Nat Neurosci Journal subject: NEUROLOGIA Year: 2018 Type: Article Affiliation country: United States
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Full text: 1 Database: MEDLINE Main subject: Genetic Predisposition to Disease / Polymorphism, Single Nucleotide / Alcoholism / Mental Disorders Type of study: Diagnostic_studies Limits: Humans Language: En Journal: Nat Neurosci Journal subject: NEUROLOGIA Year: 2018 Type: Article Affiliation country: United States