Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies.

Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, USA. Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. National Institute for Health Research Biomedical Research Centre, King's College London and South London and Maudsley National Health Service Trust, London, UK. Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. School of Psychology, Curtin University, Perth, Western Australia, Australia. School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia. Department of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. Department of Biomedicine, Aarhus University, Aarhus, Denmark. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Center for Psychiatry Research, Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden. Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Germany. Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany. Department of Medical and Molecular Genetics, King's College London, Guy's Hospital, London, UK. Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. Center for Eating Disorders Rintveld, Altrecht Mental Health Institute, Zeist, The Netherlands. Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Department of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan. NORMENT Centre, Division of Mental Health and Addiction, NORMENT Centre, University of Oslo, Oslo University Hospital, Oslo, Norway. Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany. Centre of Psychiatry and Neuroscience, INSERM U894, Paris, France. Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. Department of Medical Biology, School of Medicine, University of Split, Split, Croatia. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen University, Aachen, Germany. Klinikum Frankfurt/Oder, Frankfurt, Germany. Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Italy. Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland. Department of Biomedicine, University of Basel, Basel, Switzerland. Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Germany. Department of Molecular and Integrative Physiology, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA. Department of Emergency Psychiatry and Post-Acute Care, CHRU Montpellier, University of Montpellier, Montpellier, France. Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota, USA. Altrecht Eating Disorders Rintveld, Altrecht Mental Health Institute, Zeist, The Netherlands. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. School of Social and Community Medicine, University of Bristol, Bristol, UK. Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Hannover, Germany. Department of Nutrition and Dietetics, Harokopio University, Athens, Greece. Department of Neurosciences, University of Padova, Padova, Italy. College of Nursing, Seattle University, Seattle, Washington, USA. Department of Psychology, Virginia Commonwealth University, Richmond, Virginia, USA. College Behavioral and Emotional Health Institute, Virginia Commonwealth University, Richmond, Virginia, USA. Department of Human & Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, USA. Department of Psychiatry, Athens University Medical School, Athens University, Athens, Greece. l'institut du thorax, INSERM, CNRS, Univ Nantes, Nantes, France. Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland. Barcelona Institute of Science and Technology, Barcelona, Spain. Universitat Pompeu Fabra, Barcelona, Spain. Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Centre for Mental Health, University Hospital of Würzburg, Würzburg, Germany. Estonian Genome Center, University of Tartu, Tartu, Estonia. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. Genomics and Disease, Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Barcelona, Spain. Department of Psychiatry, University Hospital of Bellvitge -IDIBELL and CIBERobn, Barcelona, Spain. Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany. Schön Klinik Roseneck affiliated with the Medical Faculty of the University of Munich, Munich, Germany. Department of Child and Adolescent Psychiatry, University of Münster, Münster, Germany. Department of Cancer, Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic. Centre for Human Genetics, University of Marburg, Marburg, Germany. Institute of Human Genetics, School of Medicine & University Hospital Bonn, University of Bonn, Bonn, Germany. Department of Psychiatry (UPK), University of Basel, Basel, Switzerland. Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Department of Psychiatry, Psychotherapy and Psychosomatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany. 1st Psychiatric Department, National and Kapodistrian University of Athens, Medical School, Eginition Hospital, Athens, Greece. Institute of Psychiatry and Neuroscience of Paris, INSERM U1266, Paris, France. CMME (GHU Paris Psychiatrie et Neurosciences), Paris Descartes University, Paris, France. Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. Institute of Translational Genomics, Helmholtz Zentrum München - German Research Centre for Environmental Health, Neuherberg, Germany. Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland. Zorg op Orde, Delft, The Netherlands. Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg University, Heidelberg, Germany. Department of Psychiatry, and Genetics and Genomics Sciences, Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Biological Psychiatry Laboratory, McLean Hospital/Harvard Medical School, Boston, Massachusetts, USA. Eating Disorders Unit, Parklandklinik, Bad Wildungen, Germany. Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, School of Medicine, Tokai University, Isehara, Japan. Faculty of Health Sciences, Palacky University, Olomouc, Czech Republic. Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain. Department of Psychiatry, First Faculty of Medicine, Charles University, Prague, Czech Republic. Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. Eating Disorders Unit, Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria. Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, The Netherlands. Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Department of Public Health, University of Helsinki, Helsinki, Finland. Institute of Applied Health Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK. Department of Psychiatry, Seoul Paik Hospital, Inje University, Seoul, Korea. Department of Psychology, Michigan State University, East Lansing, Michigan, USA. Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway. Department of Clinical Science, Norwegian Centre for Mental Disorders Research (NORMENT), University of Bergen, Bergen, Norway. Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway. Department of Clinical Medicine, Laboratory Building, Haukeland University Hospital, Bergen, Norway. The Chicago School of Professional Psychology, Washington DC Campus, Washington, District of Columbia, USA. Department of Cancer Epidemiology and Prevention, M Skłodowska-Curie Cancer Center - Oncology Center, Warsaw, Poland. BESE Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia. Department of Psychiatry, University of Lausanne-University Hospital of Lausanne (UNIL-CHUV), Lausanne, Switzerland. Department of Psychiatry, University of Campania "Luigi Vanvitelli", Naples, Italy. Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland. Department of Paediatric Laboratory Medicine, Division of Genome Diagnostics, The Hospital for Sick Children, Toronto, Ontario, Canada. NORMENT KG Jebsen Centre, Division of Mental Health and Addiction, University of Oslo, Oslo University Hospital, Oslo, Norway. Department of Psychiatry, University College Cork, Cork, Ireland. Eist Linn Adolescent Unit, Bessborough, Health Service Executive South, Cork, Ireland. Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. Molecular Epidemiology Section (Department of Biomedical Datasciences), Leiden University Medical Centre, Leiden, The Netherlands. Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland. Division of Child and Adolescent Psychiatry, Geneva University Hospital, Geneva, Switzerland. National Center for PTSD, VA Boston Healthcare System, Boston, Massachusetts, USA. Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts, USA. Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Italy. Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy. Kartini Clinic, Portland, Oregon, USA. Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, California, USA. Department of Psychiatry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. Department of Medicine, Center for Molecular Medicine, Division of Rheumatology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. Institute for Molecular Medicine FIMM, HiLIFE, University of Helsinki, Helsinki, Finland. Center for Human Genome Research, Massachusetts General Hospital, Boston, Massachusetts, USA. Saint Joan de Déu Research Institute, Saint Joan de Déu Barcelona Children's Hospital, Barcelona, Spain. Institute of Biomedicine (IBUB), University of Barcelona, Barcelona, Spain. Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain. Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Department of Health Science, University of Florence, Florence, Italy. Department of Biometry, University of Helsinki, Helsinki, Finland. Department of Child and Adolescent Psychiatry, Faculty of Medicine, Eating Disorders Research and Treatment Center, Technische Universität Dresden, Dresden, Germany. Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnologies, University of Pisa, Pisa, Italy. Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland. Department of Neurosciences, Padua Neuroscience Center, University of Padova, Padova, Italy. Institute of Medical Statistics, Computer and Data Sciences, Jena University Hospital, Jena, Germany. Department of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada. Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. J. Craig Venter Institute (JCVI), La Jolla, California, USA. Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria. Department of Pediatrics and Center of Applied Genomics, First Faculty of Medicine, Charles University, Prague, Czech Republic. Molecular Epidemiology Section (Department of Medical Statistics), Leiden University Medical Centre, Leiden, The Netherlands. Center for Eating Disorders Ursula, Rivierduinen, Leiden, The Netherlands. Department of Psychiatry, Leiden University Medical Centre, Leiden, The Netherlands. Department of Child and Adolescent Psychiatry, Poznan University of Medical Sciences, Poznan, Poland. IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy. Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland. Department of Psychiatry, University of Naples SUN, Naples, Italy. Department of Psychiatry, University of Perugia, Perugia, Italy. Brain Sciences Department, Stremble Ventures, Limassol, Cyprus. Adolescent Health Unit, Second Department of Pediatrics, "P. & A. Kyriakou" Children's Hospital, University of Athens, Athens, Greece. Pediatric Intensive Care Unit, "P. & A. Kyriakou" Children's Hospital, University of Athens, Athens, Greece. Faculty of Social and Behavioral Sciences, Utrecht University, Utrecht, The Netherlands. Department of Internal Medicine VI, Psychosomatic Medicine and Psychotherapy, University Medical Hospital Tuebingen, Tuebingen, Germany. BioRealm, LLC, Walnut, California, USA. Oregon Research Institute, Eugene, Oregon, USA. Christchurch Health and Development Study, University of Otago, Christchurch, New Zealand. The Center for Eating Disorders at Sheppard Pratt, Baltimore, Maryland, USA. Department of Psychiatry, Weill Cornell Medical College, New York, New York, USA. Eating Recovery Center, Denver, Colorado, USA. Department of Psychiatry, University of California San Diego, La Jolla, California, USA. Department of Psychiatry and Behavioral Science, University of North Dakota School of Medicine and Health Sciences, Fargo, North Dakota, USA. Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Biostatistics and Computational Biology Unit, University of Otago, Christchurch, New Zealand. Department of Psychiatry and Biobehavioral Science, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, California, USA. David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. Centre for Mental Health, University Health Network, Toronto, Ontario, Canada. Program for Eating Disorders, University Health Network, Toronto, Ontario, Canada. The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark. Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark. Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark. Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. National Centre for Register-Based Research, Aarhus BSS, Aarhus University, Aarhus, Denmark. Centre for Integrated Register-based Research (CIRRAU), Aarhus University, Aarhus, Denmark. Department of Psychological Medicine, University of Otago, Christchurch, New Zealand. Canterbury District Health Board, Christchurch, New Zealand. Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. Department of Psychiatry, Division of Human Genetics, Yale School of Medicine, New Haven, Connecticut, USA. Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA. Faculty of Business, Karabuk University, Karabuk, Turkey. Virginia Commonwealth University Alcohol Research Center, Virginia Commonwealth University, Richmond, Virginia, USA. Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, USA. Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia, USA. Psychiatric Genomics and Pharmacogenomics Program, Mayo Clinic, Rochester, Minnesota, USA. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA. Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, New York, USA. Division of Psychiatry, University of Edinburgh, Edinburgh, UK. Institute of Human Genetics, University of Bonn School of Medicine & University Hospital Bonn, Bonn, Germany. Department of Psychiatry, University of Utah, Salt Lake City, Utah, USA. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Laboratory of Neurogenetics, NIH/NIAAA, Bethesda, Maryland, USA. Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland. Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. Turku Institute for Advanced Studies, University of Turku, Turku, Finland. Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA. Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. Division of Psychiatry, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, USA. Department of Psychiatry and Behavioral Sciences, Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, New York, USA. Department of Psychiatry, Amsterdam Public Health Research Institute, VU University Medical Center/GGz inGeest, Amsterdam, The Netherlands. Department of Genetics, Washington University School of Medicine, Saint Louis, Missouri, USA. Office of the Clinical Director, NIH/NIAAA, Bethesda, Maryland, USA. Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts, USA. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Cambridge, Massachusetts, USA. Department of Sociology, Harvard University, Cambridge, Massachusetts, USA. Department of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado, USA. Institute of Behavioral Science, University of Colorado, Boulder, Colorado, USA. Department of Sociology, University of Colorado, Boulder, Colorado, USA. Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA. Department of Psychiatry, University of Vermont Medical Center, Burlington, Vermont, USA. Department of Medicine, Division of Biostatistics, Washington University School of Medicine, Saint Louis, Missouri, USA. Department of Psychiatry, University of Mainz, Mainz, Germany. National Drug and Alcohol Research Centre, University of New South Wales, Sydney, New South Wales, Australia. Stanford University Graduate School of Education, Stanford University, Stanford, California, USA. Department of Psychiatry and Psychotherapy, University of Düsseldorf, Duesseldorf, Germany. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. Max-Planck-Institute of Psychiatry, Munich, Germany. Department of Psychology, University of Minnesota, Minneapolis, Minnesota, USA. Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany. Department of Psychiatry, University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, Iowa, USA. Addictions Department, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. Department of Psychiatry, University of Bonn, Bonn, Germany. Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland. Department of Statistical Genetics, Max-Planck-Institute of Psychiatry, München, Germany. Aberdeen Biomedical Imaging Centre, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Foresterhill, Aberdeen, UK. Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA. Department of Psychiatry, Psychotherapy and Psychosomatics, Martin-Luther-University Halle-Wittenberg, Herborn, Germany. Department of Psychiatry and Psychotherapy, Vitos Hospital Herborn, Herborn, Germany. School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Department of Psychiatry and Psychotherapy, University of Regensburg Psychiatric Health Care Aargau, Regensburg, Germany. Department of Psychiatry and Psychotherapy and Department of Addictive Behaviour and Addiction Medicine, Medical Faculty, LVR-Hospital Essen, University of Duisburg-Essen, Essen, Germany. Medical Park Chiemseeblick in Bernau-Felden, Ludwig-Maximilians-University, Bernau am Chiemsee, Germany. Psychiatric Hospital, Ludwig-Maximilians-University, Bernau am Chiemsee, Germany. Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany. Department of Psychiatry, Psychiatric Hospital, Ludwig-Maximilians-University, Munich, Germany. Department of Sociology, University of Utah, Salt Lake City, Utah, USA. Department of Psychology, University of California San Diego, La Jolla, California, USA. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA. Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois, USA. NIAAA Intramural Research Program, Bethesda, Maryland, USA. Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland. National Institute for Health and Welfare, Helsinki, Finland. Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA. Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, USA. Department of Epidemiology, School of Public Health, Boston University, Boston, Massachusetts, USA. Department of Biostatistics, School of Public Health, Boston University, Boston, Massachusetts, USA. Office of the Clinical Director, NIH/NIAAA, Besthesda, Maryland, USA. Center for Omics Discovery and Epidemiology, Behavioral Health Research Division, RTI International, Research Triangle Park, North Carolina, USA. Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. Department of Psychiatry, University of Connecticut School of Medicine, Farmington, Connecticut, USA. Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, USA. Department of Psychiatry, University of Colorado Denver, Aurora, Colorado, USA. Fellow Program, RTI International, Research Triangle Park, North Carolina, USA. Center for Studies of Addiction, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. VISN 4 MIRECC, Crescenz VAMC, Philadelphia, Pennsylvania, USA. Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, USA. Peter Boris Centre for Addictions Research, McMaster University/St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada. Michael G. DeGroote Centre for Medicinal Cannabis Research, McMaster University/St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada. Institute for Genomic Medicine, University of California San Diego, La Jolla, California, USA. Department of Psychiatry, Amsterdam UMC, VU University and GGZinGeest, Amsterdam, The Netherlands. Department of Psychological & Brain Sciences, Indiana University Bloomington, Bloomington, Indiana, USA. Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, Connecticut, USA. School of Psychology, Flinders University, Adelaide, South Australia, Australia. Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. Department of Genetics, Yale School of Medicine, New Haven, Connecticut, USA. Department of Neuroscience, Yale School of Medicine, New Haven, Connecticut, USA. Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Addiction biology. 2021;(1):e12880

Abstract

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.