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.

1st Psychiatric Department National and Kapodistrian University of Athens Medical School Eginition Hospital Athens Greece

Aberdeen Biomedical Imaging Centre School of Medicine Medical Sciences and Nutrition University of Aberdeen Foresterhill Aberdeen UK

Addictions Department Institute of Psychiatry Psychology and Neuroscience King's College London London UK

Adolescent Health Unit 2nd Department of Pediatrics P and A Kyriakou Children's Hospital University of Athens Athens Greece

Altrecht Eating Disorders Rintveld Altrecht Mental Health Institute Zeist The Netherlands

Analytic and Translational Genetics Unit Department of Medicine Massachusetts General Hospital and Harvard Medical School Boston Massachusetts USA

Barcelona Institute of Science and Technology Barcelona Spain

BESE Division King Abdullah University of Science and Technology Thuwal Saudi Arabia

Bioinformatics Research Centre Aarhus University Aarhus Denmark

Biological Psychiatry Laboratory McLean Hospital Harvard Medical School Boston Massachusetts USA

BioRealm LLC Walnut California USA

Biostatistics and Computational Biology Unit University of Otago Christchurch New Zealand

Brain Sciences Department Stremble Ventures Limassol Cyprus

Canterbury District Health Board Christchurch New Zealand

Carolina Population Center University of North Carolina at Chapel Hill Chapel Hill North Carolina USA

Center for Applied Genomics Children's Hospital of Philadelphia Philadelphia Pennsylvania USA

Center for Eating Disorders Rintveld Altrecht Mental Health Institute Zeist The Netherlands

Center for Eating Disorders Ursula Rivierduinen Leiden The Netherlands

Center for Human Genome Research Massachusetts General Hospital Boston Massachusetts USA

Center for Integrative Genomics University of Lausanne Lausanne Switzerland

Center for Neurobehavioral Genetics Semel Institute for Neuroscience and Human Behavior University of California Los Angeles Los Angeles California USA

Center for Omics Discovery and Epidemiology Behavioral Health Research Division RTI International Research Triangle Park North Carolina USA

Center for Psychiatry Research Stockholm Health Care Services Stockholm County Council Stockholm Sweden

Center for Studies of Addiction University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA

Centre for Addiction and Mental Health Toronto Ontario Canada

Centre for Human Genetics University of Marburg Marburg Germany

Centre for Integrated Register based Research Aarhus University Aarhus Denmark

Centre for Integrative Sequencing iSEQ Aarhus University Aarhus Denmark

Centre for Mental Health University Health Network Toronto Ontario Canada

Centre of Psychiatry and Neuroscience INSERM U894 Paris France

Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública Barcelona Spain

Christchurch Health and Development Study University of Otago Christchurch New Zealand

Clinical Genetics Unit Department of Woman and Child Health University of Padova Italy

CMME Paris Descartes University Paris France

College Behavioral and Emotional Health Institute Virginia Commonwealth University Richmond Virginia USA

College of Nursing Seattle University Seattle Washington USA

David Geffen School of Medicine University of California Los Angeles Los Angeles California USA

Department of Addictive Behavior and Addiction Medicine Central Institute of Mental Health Medical Faculty Mannheim Heidelberg University Mannheim Germany

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Department of Child and Adolescent Psychiatry Faculty of Medicine Eating Disorders Research and Treatment Center Technische Universität Dresden Dresden Germany

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Department of Genetics University of North Carolina at Chapel Hill Chapel Hill North Carolina USA

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Department of Psychiatry Psychotherapy and Psychosomatics Martin Luther University Halle Wittenberg Halle Germany

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Department of Psychiatry Seoul Paik Hospital Inje University Seoul Korea

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Department of Psychiatry University of Mainz Mainz Germany

Department of Psychiatry University of Minnesota Minneapolis Minnesota USA

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Department of Psychology and Logopedics University of Helsinki Helsinki Finland

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Department of Sociology University of Utah Salt Lake City Utah USA

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Estonian Genome Center University of Tartu Tartu Estonia

Faculty of Business Karabuk University Karabuk Turkey

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Groningen Institute for Evolutionary Life Sciences University of Groningen Groningen The Netherlands

Human Genomics Research Group Department of Biomedicine University of Basel Basel Switzerland

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Institute of Applied Health Sciences School of Medicine Medical Sciences and Nutrition University of Aberdeen Aberdeen UK

Institute of Behavioral Science University of Colorado Boulder Colorado USA

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Institute of Human Genetics School of Medicine and University Hospital Bonn University of Bonn Bonn Germany

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Institute of Translational Genomics Helmholtz Zentrum München German Research Centre for Environmental Health Neuherberg Germany

IRCCS Fondazione Don Carlo Gnocchi Florence Italy

J Craig Venter Institute La Jolla California USA

Johns Hopkins Bloomberg School of Public Health Baltimore Maryland USA

Kartini Clinic Portland Oregon USA

Klinikum Frankfurt Oder Frankfurt Germany

l'institut du thorax INSERM CNRS Univ Nantes Nantes France

Laboratory of Neurogenetics NIH NIAAA Bethesda Maryland USA

Max Planck Institute of Psychiatry Munich Germany

McLaughlin Centre University of Toronto Toronto Ontario Canada

Medical Park Chiemseeblick in Bernau Felden Ludwig Maximilians University Bernau am Chiemsee Germany

Michael G DeGroote Centre for Medicinal Cannabis Research McMaster University St Joseph's Healthcare Hamilton Hamilton Ontario Canada

Molecular Epidemiology Section Leiden University Medical Centre Leiden The Netherlands

MRC Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh UK

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National Center for PTSD VA Boston Healthcare System Boston Massachusetts USA

National Centre for Register Based Research Aarhus BSS Aarhus University Aarhus Denmark

National Drug and Alcohol Research Centre University of New South Wales Sydney New South Wales Australia

National Institute for Health and Welfare Helsinki Finland

National Institute for Health Research Biomedical Research Centre King's College London and South London and Maudsley National Health Service Trust London UK

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Office of the Clinical Director NIH NIAAA Bethesda Maryland USA

Oregon Research Institute Eugene Oregon USA

Pediatric Intensive Care Unit P and A Kyriakou Children's Hospital University of Athens Athens Greece

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Psychiatric Genomics and Pharmacogenomics Program Mayo Clinic Rochester Minnesota USA

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Schön Klinik Roseneck affiliated with the Medical Faculty of the University of Munich Munich Germany

School of Paediatrics and Child Health University of Western Australia Perth Western Australia Australia

School of Pharmacy University of Pittsburgh Pittsburgh Pennsylvania USA

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School of Psychology Flinders University Adelaide South Australia Australia

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Social Genetic and Developmental Psychiatry Centre Institute of Psychiatry Psychology and Neuroscience King's College London London UK

Stanford University Graduate School of Education Stanford University Stanford California USA

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