Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.

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

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

American School of Professional Psychology Argosy University Northern Virginia Arlington VA USA

Analytic and Translational Genetics Unit Massachusetts General Hospital Boston MA 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 MA USA

BioRealm LLC Walnut CA USA

Biostatistics and Computational Biology Unit University of Otago Christchurch New Zealand

Brain Center Rudolf Magnus Department of Translational Neuroscience University Medical Center Utrecht Utrecht the Netherlands

Brain Sciences Department Stremble Ventures Limassol Cyprus

Canterbury District Health Board Christchurch New Zealand

Center for Applied Genomics Children's Hospital of Philadelphia Philadelphia PA 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 at the Massachusetts General Hospital Boston MA 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 CA USA

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

Centre for Addiction and Mental Health Toronto Ontario Canada

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

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 Padova Italy

CMME Hôpital Sainte Anne Paris Descartes University Paris France

College of Nursing Seattle University Seattle WA USA

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

Department of Adult Psychiatry Poznan University of Medical Sciences Poznan Poland

Department of Behavioral Medicine National Institute of Mental Health National Center of Neurology and Psychiatry Tokyo Japan

Department of Biomedical Data Science Leiden University Medical Centre Leiden the Netherlands

Department of Biomedicine Aarhus University Aarhus Denmark

Department of Biomedicine University of Basel Basel Switzerland

Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Cancer Epidemiology and Prevention M Skłodowska Curie Cancer Center Oncology Center Warsaw Poland

Department of Cell Biology and Physiology University of North Carolina at Chapel Hill Chapel Hill NC USA

Department of Child and Adolescent Psychiatry Klinikum Frankfurt Oder Frankfurt Germany

Department of Child and Adolescent Psychiatry Poznan University of Medical Sciences Poznan Poland

Department of Child and Adolescent Psychiatry Psychosomatics and Psychotherapy RWTH Aachen University Aachen Germany

Department of Child and Adolescent Psychiatry Psychosomatics and Psychotherapy University Hospital of Würzburg Centre for Mental Health Würzburg Germany

Department of Child and Adolescent Psychiatry University Hospital Essen University of Duisburg Essen Essen Germany

Department of Clinical Medicine Laboratory Building Haukeland University Hospital Bergen Norway

Department of Clinical Medicine University of Copenhagen Copenhagen Denmark

Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden

Department of Clinical Science K G Jebsen Centre for Psychosis Research Norwegian Centre for Mental Disorders Research University of Bergen Bergen Norway

Department of Clinical Sciences School of Medicine University of Barcelona Barcelona Spain

Department of Emergency Psychiatry and Post Acute Care CHRU Montpellier University of Montpellier Montpellier France

Department of Environmental Epidemiology Nofer Institute of Occupational Medicine Lodz Poland

Department of General Internal Medicine and Psychosomatics Heidelberg University Hospital Heidelberg University Heidelberg Germany

Department of Genetics and Genomic Biology The Hospital for Sick Children Toronto Ontario Canada

Department of Genetics Microbiology and Statistics University of Barcelona Barcelona Spain

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

Department of Genomics Life and Brain Center University of Bonn Bonn Germany

Department of Health Science University of Florence Florence Italy

Department of Internal Medicine 6 Psychosomatic Medicine and Psychotherapy University Medical Hospital Tuebingen Tuebingen Germany

Department of Medical and Molecular Genetics King's College London Guy's Hospital London UK

Department of Medical Biology School of Medicine University of Split Split Croatia

Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden

Department of Medicine Surgery and Dentistry Scuola Medica Salernitana University of Salerno Salerno Italy

Department of Mental Disorders Norwegian Institute of Public Health Oslo Norway

Department of Molecular Life Science Division of Basic Medical Science and Molecular Medicine School of Medicine Tokai University Isehara Japan

Department of Neuroscience Psychology Drug Research and Child Health University of Florence Florence Italy

Department of Neurosciences Padua Neuroscience Center University of Padova Padova Italy

Department of Neurosciences University of Padova Padova Italy

Department of Nutrition and Dietetics Harokopio University Athens Greece

Department of Nutrition University of North Carolina at Chapel Hill Chapel Hill NC USA

Department of Paediatric Laboratory Medicine The Hospital for Sick Children Toronto Ontario Canada

Department of Pathology and Biomedical Science University of Otago Christchurch New Zealand

Department of Pediatrics and Center of Applied Genomics 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Pediatrics Perelman School of Medicine University of Pennsylvania Philadelphia PA USA

Department of Psychiatric Genetics Poznan University of Medical Sciences Poznan Poland

Department of Psychiatry 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Psychiatry and Behavioral Science University of North Dakota School of Medicine and Health Sciences Fargo ND USA

Department of Psychiatry and Behavioral Sciences Stanford University Stanford CA USA

Department of Psychiatry and Biobehavioral Science Semel Institute for Neuroscience and Human Behavior University of California Los Angeles Los Angeles CA USA

Department of Psychiatry and Genetics and Genomics Sciences Division of Psychiatric Genomics Icahn School of Medicine at Mount Sinai New York NY USA

Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology Sahlgrenska Academy at the University of Gothenburg Gothenburg Sweden

Department of Psychiatry and Psychotherapy Charité Universitätsmedizin Berlin Germany

Department of Psychiatry and Psychotherapy Ludwig Maximilians University Munich Germany

Department of Psychiatry and Psychotherapy Medical University of Vienna Vienna Austria

Department of Psychiatry Athens University Medical School Athens University Athens Greece

Department of Psychiatry Center for Neurobiology and Behavior Perelman School of Medicine at the University of Pennsylvania Philadelphia PA USA

Department of Psychiatry Faculty of Medicine University of Geneva Geneva Switzerland

Department of Psychiatry Leiden University Medical Centre Leiden the Netherlands

Department of Psychiatry Neurobiology Pharmacology and Biotechnologies University of Pisa Pisa Italy

Department of Psychiatry Poznan University of Medical Sciences Poznan Poland

Department of Psychiatry Psychosomatics and Psychotherapy University of Würzburg Würzburg Germany

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

Department of Psychiatry Seoul Paik Hospital Inje University Seoul Korea

Department of Psychiatry University College Cork Cork Ireland

Department of Psychiatry University Hospital of Bellvitge IDIBELL and CIBERobn Barcelona Spain

Department of Psychiatry University of Basel Basel Switzerland

Department of Psychiatry University of California San Diego San Diego CA USA

Department of Psychiatry University of Campania Luigi Vanvitelli Naples Italy

Department of Psychiatry University of Lausanne University Hospital of Lausanne Lausanne Switzerland

Department of Psychiatry University of Minnesota Minneapolis MN USA

Department of Psychiatry University of Naples SUN Naples Italy

Department of Psychiatry University of North Carolina at Chapel Hill Chapel Hill NC USA

Department of Psychiatry University of Perugia Perugia Italy

Department of Psychiatry University of Toronto Toronto Ontario Canada

Department of Psychiatry Weill Cornell Medical College New York NY USA

Department of Psychological Medicine University of Otago Christchurch New Zealand

Department of Psychology Michigan State University East Lansing MI USA

Department of Psychology Virginia Commonwealth University Richmond VA USA

Department of Psychosomatic Medicine and Psychotherapy Hannover Medical School Hannover Germany

Department of Public Health University of Helsinki Helsinki Finland

Department of Surgery Faculty of Medicine University of Toronto Toronto Ontario Canada

Division of Child and Adolescent Psychiatry Geneva University Hospital Geneva Switzerland

Division of Psychological and Social Medicine and Developmental Neurosciences Faculty of Medicine Technische Universität Dresden Dresden Germany

Dr Einar Martens Research Group for Biological Psychiatry Center for Medical Genetics and Molecular Medicine Haukeland University Hospital Bergen Norway

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

Eating Disorders Unit Department of Child and Adolescent Psychiatry Medical University of Vienna Vienna Austria

Eating Disorders Unit Parklandklinik Bad Wildungen Germany

Eating Recovery Center Denver CO USA

Estonian Genome Center University of Tartu Tartu Estonia

Faculty of Health Sciences Palacky University Olomouc Czech Republic

Faculty of Medicine and Health Sciences University of Aukland Aukland New Zealand

Faculty of Social and Behavioral Sciences Utrecht University Utrecht the Netherlands

Genomics and Disease Bioinformatics and Genomics Programme Centre for Genomic Regulation Barcelona Spain

Great Ormond Street Institute of Child Health University College London London UK

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

HSE National Clinical Programme for Eating Disorders Cork Ireland

INSERM 1266 Institute of Psychiatry and Neuroscience of Paris Paris France

Institute for Molecular Bioscience University of Queensland Brisbane Queensland Australia

Institute for Molecular Medicine Finland Helsinki Institute of Life Science University of Helsinki Helsinki Finland

Institute for Molecular Medicine Finland HiLIFE Unit University of Helsinki Helsinki Finland

Institute of Applied Health Sciences University of Aberdeen Aberdeen UK

Institute of Biomedicine University of Barcelona Barcelona Spain

Institute of Clinical Medicine University of Oslo Oslo Norway

Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden

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

Institute of Medical Genetics and Pathology University Hospital Basel Basel Switzerland

Institute of Medical Science University of Toronto Toronto Ontario Canada

Institute of Medical Statistics Computer and Data Sciences Jena University Hospital Jena Germany

Institute of Molecular and Cell Biology University of Tartu Tartu Estonia

Institute of Neuroscience and Physiology Sahlgrenska Academy at the University of Gothenburg Gothenburg Sweden

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

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

Institute of Public Health and Clinical Nutrition Department of Clinical Nutrition University of Eastern Finland Kuopio Finland

Institute of Translational Genomics Helmholtz Zentrum München Neuherberg Germany

IRCSS Fondazione Don Carlo Gnocchi Florence Italy

J Craig Venter Institute La Jolla CA USA

Kartini Clinic Portland OR USA

L'institut du thorax INSERM CNRS UNIV Nantes CHU Nantes Nantes France

Life Sciences Institute and Department of Molecular and Integrative Physiology University of Michigan Ann Arbor MI USA

MRC Integrative Epidemiology Unit University of Bristol Bristol UK

National Center for PTSD VA Boston Healthcare System Department of Psychiatry Boston University School of Medicine Boston MA USA

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

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

NORMENT KG Jebsen Centre Division of Mental Health and Addiction University of Oslo Oslo University Hospital Oslo Norway

Oregon Research Institute Eugene OR USA

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

Program for Eating Disorders University Health Network Toronto Ontario Canada

Program in Medical and Population Genetics Broad Institute of the Massachusetts Institute of Technology and Harvard University Cambridge MA USA

QIMR Berghofer Medical Research Institute Brisbane Queensland Australia

Queensland Brain Institute University of Queensland Brisbane Queensland Australia

Rheumatology Research Group Vall d'Hebron Research Institute Barcelona Spain

Rheumatology Unit Department of Medicine Center for Molecular Medicine Karolinska Institutet and Karolinska University Hospital Stockholm Sweden

Saint Joan de Déu Research Institute Saint Joan de Déu Barcelona Children's Hospital Barcelona Spain

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 Psychology Curtin University Perth Western Australia Australia

School of Psychology Flinders University Adelaide South Australia Australia

School of Social and Community Medicine University of Bristol Bristol UK

Stanley Center for Psychiatric Research Broad Institute of the Massachusetts Institute of Technology and Harvard University Cambridge MA USA

The Center for Eating Disorders at Sheppard Pratt Baltimore MD USA

The Lundbeck Foundation Initiative for Integrative Psychiatric Research Aarhus Denmark

Universitat Pompeu Fabra Barcelona Spain

Wellcome Sanger Institute Hinxton UK

Zorg op Orde Leidschendam the Netherlands

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