. 2019 Aug;51(8):1207-1214.

doi: 10.1038/s41588-019-0439-2. Epub 2019 Jul 15.

Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Hunna J Watson^{1

2

3}, Zeynep Yilmaz^{1

4}, Laura M Thornton¹, Christopher Hübel^{5

6}, Jonathan R I Coleman^{5

7}, Héléna A Gaspar^{5

7}, Julien Bryois⁶, Anke Hinney⁸, Virpi M Leppä⁶, Manuel Mattheisen^{9

10

11

12}, Sarah E Medland¹³, Stephan Ripke^{14

15

16}, Shuyang Yao⁶, Paola Giusti-Rodríguez⁴; Anorexia Nervosa Genetics Initiative; Ken B Hanscombe¹⁷, Kirstin L Purves⁵; Eating Disorders Working Group of the Psychiatric Genomics Consortium; Roger A H Adan^{18

19

20}, Lars Alfredsson²¹, Tetsuya Ando²², Ole A Andreassen²³, Jessica H Baker¹, Wade H Berrettini²⁴, Ilka Boehm²⁵, Claudette Boni²⁶, Vesna Boraska Perica^{27

28}, Katharina Buehren²⁹, Roland Burghardt³⁰, Matteo Cassina³¹, Sven Cichon³², Maurizio Clementi³¹, Roger D Cone³³, Philippe Courtet³⁴, Scott Crow³⁵, James J Crowley^{4

10}, Unna N Danner¹⁹, Oliver S P Davis^{36

37}, Martina de Zwaan³⁸, George Dedoussis³⁹, Daniela Degortes⁴⁰, Janiece E DeSocio⁴¹, Danielle M Dick⁴², Dimitris Dikeos⁴³, Christian Dina⁴⁴, Monika Dmitrzak-Weglarz⁴⁵, Elisa Docampo^{46

47

48}, Laramie E Duncan⁴⁹, Karin Egberts⁵⁰, Stefan Ehrlich²⁵, Geòrgia Escaramís^{46

47

48}, Tõnu Esko^{51

52}, Xavier Estivill^{46

47

48

53}, Anne Farmer⁵, Angela Favaro⁴⁰, Fernando Fernández-Aranda^{54

55}, Manfred M Fichter^{56

57}, Krista Fischer⁵¹, Manuel Föcker⁸, Lenka Foretova⁵⁸, Andreas J Forstner^{32

59

60

61

62}, Monica Forzan³¹, Christopher S Franklin²⁷, Steven Gallinger⁶³, Ina Giegling⁶⁴, Johanna Giuranna⁸, Fragiskos Gonidakis⁶⁵, Philip Gorwood^{26

66}, Monica Gratacos Mayora^{46

47

48}, Sébastien Guillaume³⁴, Yiran Guo⁶⁷, Hakon Hakonarson^{67

68}, Konstantinos Hatzikotoulas^{27

69}, Joanna Hauser⁷⁰, Johannes Hebebrand⁸, Sietske G Helder^{5

71}, Stefan Herms^{32

60

62}, Beate Herpertz-Dahlmann²⁹, Wolfgang Herzog⁷², Laura M Huckins^{27

73}, James I Hudson⁷⁴, Hartmut Imgart⁷⁵, Hidetoshi Inoko⁷⁶, Vladimir Janout⁷⁷, Susana Jiménez-Murcia^{54

55}, Antonio Julià⁷⁸, Gursharan Kalsi⁵, Deborah Kaminská⁷⁹, Jaakko Kaprio^{80

81}, Leila Karhunen⁸², Andreas Karwautz⁸³, Martien J H Kas^{18

84}, James L Kennedy^{85

86

87}, Anna Keski-Rahkonen⁸⁰, Kirsty Kiezebrink⁸⁸, Youl-Ri Kim⁸⁹, Lars Klareskog⁹⁰, Kelly L Klump⁹¹, Gun Peggy S Knudsen⁹², Maria C La Via¹, Stephanie Le Hellard^{93

94

95}, Robert D Levitan^{85

86

87}, Dong Li⁶⁷, Lisa Lilenfeld⁹⁶, Bochao Danae Lin¹⁸, Jolanta Lissowska⁹⁷, Jurjen Luykx¹⁸, Pierre J Magistretti^{98

99}, Mario Maj¹⁰⁰, Katrin Mannik^{51

101}, Sara Marsal⁷⁸, Christian R Marshall¹⁰², Morten Mattingsdal²³, Sara McDevitt^{103

104}, Peter McGuffin⁵, Andres Metspalu^{51

105}, Ingrid Meulenbelt¹⁰⁶, Nadia Micali^{107

108

109}, Karen Mitchell¹¹⁰, Alessio Maria Monteleone¹⁰⁰, Palmiero Monteleone¹¹¹, Melissa A Munn-Chernoff¹, Benedetta Nacmias¹¹², Marie Navratilova⁵⁸, Ioanna Ntalla³⁹, Julie K O'Toole¹¹³, Roel A Ophoff^{18

114}, Leonid Padyukov⁹⁰, Aarno Palotie^{52

81

115}, Jacques Pantel²⁶, Hana Papezova⁷⁹, Dalila Pinto⁷³, Raquel Rabionet^{116

117

118}, Anu Raevuori⁸⁰, Nicolas Ramoz²⁶, Ted Reichborn-Kjennerud^{92

119}, Valdo Ricca^{112

120}, Samuli Ripatti^{52

80

121}, Franziska Ritschel^{25

122}, Marion Roberts^{5

123

124}, Alessandro Rotondo¹²⁵, Dan Rujescu^{56

64}, Filip Rybakowski¹²⁶, Paolo Santonastaso¹²⁷, André Scherag¹²⁸, Stephen W Scherer¹²⁹, Ulrike Schmidt^{7

130}, Nicholas J Schork¹³¹, Alexandra Schosser¹³², Jochen Seitz²⁹, Lenka Slachtova¹³³, P Eline Slagboom¹⁰⁶, Margarita C T Slof-Op 't Landt^{134

135}, Agnieszka Slopien¹³⁶, Sandro Sorbi^{112

137}, Beata Świątkowska¹³⁸, Jin P Szatkiewicz⁴, Ioanna Tachmazidou²⁷, Elena Tenconi⁴⁰, Alfonso Tortorella^{139

140}, Federica Tozzi¹⁴¹, Janet Treasure^{7

130}, Artemis Tsitsika¹⁴², Marta Tyszkiewicz-Nwafor¹³⁶, Konstantinos Tziouvas¹⁴³, Annemarie A van Elburg^{19

144}, Eric F van Furth^{134

135}, Gudrun Wagner⁸³, Esther Walton²⁵, Elisabeth Widen⁸¹, Eleftheria Zeggini^{27

69}, Stephanie Zerwas¹, Stephan Zipfel¹⁴⁵, Andrew W Bergen^{146

147}, Joseph M Boden¹⁴⁸, Harry Brandt¹⁴⁹, Steven Crawford¹⁴⁹, Katherine A Halmi¹⁵⁰, L John Horwood¹⁴⁸, Craig Johnson¹⁵¹, Allan S Kaplan^{85

86

87}, Walter H Kaye¹⁵², James E Mitchell¹⁵³, Catherine M Olsen¹³, John F Pearson¹⁵⁴, Nancy L Pedersen⁶, Michael Strober^{155

156}, Thomas Werge¹⁵⁷, David C Whiteman¹³, D Blake Woodside^{86

87

158

159}, Garret D Stuber^{1

160}, Scott Gordon¹³, Jakob Grove^{9

161

162

163}, Anjali K Henders¹⁶⁴, Anders Juréus⁶, Katherine M Kirk¹³, Janne T Larsen^{161

165

166}, Richard Parker¹³, Liselotte Petersen^{161

165

166}, Jennifer Jordan^{123

167}, Martin Kennedy¹⁶⁸, Grant W Montgomery^{13

164

169}, Tracey D Wade¹⁷⁰, Andreas Birgegård^{10

11}, Paul Lichtenstein⁶, Claes Norring^{10

11}, Mikael Landén^{6

171}, Nicholas G Martin¹³, Preben Bo Mortensen^{161

165

166}, Patrick F Sullivan^{1

4

6}, Gerome Breen^{5

7}, Cynthia M Bulik^{172

173

174}

Affiliations

¹ Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
² School of Psychology, Curtin University, Perth, Western Australia, Australia.
³ School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia.
⁴ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵ Institute of Psychiatry, Psychology and Neuroscience, Social, Genetic and Developmental Psychiatry (SGDP) Centre, King's College London, London, UK.
⁶ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁷ National Institute for Health Research Biomedical Research Centre, King's College London and South London and Maudsley National Health Service Foundation Trust, London, UK.
⁸ Department of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
⁹ Department of Biomedicine, Aarhus University, Aarhus, Denmark.
¹⁰ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
¹¹ Center for Psychiatry Research, Stockholm Health Care Services, Stockholm City Council, Stockholm, Sweden.
¹² Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
¹³ QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
¹⁴ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
¹⁵ Stanley Center for Psychiatric Research, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
¹⁶ Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany.
¹⁷ Department of Medical and Molecular Genetics, King's College London, Guy's Hospital, London, UK.
¹⁸ Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
¹⁹ Center for Eating Disorders Rintveld, Altrecht Mental Health Institute, Zeist, the Netherlands.
²⁰ Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
²¹ Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
²² Department of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.
²³ NORMENT KG Jebsen Centre, Division of Mental Health and Addiction, University of Oslo, Oslo University Hospital, Oslo, Norway.
²⁴ Department of Psychiatry, Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
²⁵ Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
²⁶ INSERM 1266, Institute of Psychiatry and Neuroscience of Paris, Paris, France.
²⁷ Wellcome Sanger Institute, Hinxton, UK.
²⁸ Department of Medical Biology, School of Medicine, University of Split, Split, Croatia.
²⁹ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen University, Aachen, Germany.
³⁰ Department of Child and Adolescent Psychiatry, Klinikum Frankfurt/Oder, Frankfurt, Germany.
³¹ Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy.
³² Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
³³ Life Sciences Institute and Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
³⁴ Department of Emergency Psychiatry and Post-Acute Care, CHRU Montpellier, University of Montpellier, Montpellier, France.
³⁵ Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
³⁶ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
³⁷ School of Social and Community Medicine, University of Bristol, Bristol, UK.
³⁸ Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Hannover, Germany.
³⁹ Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
⁴⁰ Department of Neurosciences, University of Padova, Padova, Italy.
⁴¹ College of Nursing, Seattle University, Seattle, WA, USA.
⁴² Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA.
⁴³ Department of Psychiatry, Athens University Medical School, Athens University, Athens, Greece.
⁴⁴ L'institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France.
⁴⁵ Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland.
⁴⁶ Barcelona Institute of Science and Technology, Barcelona, Spain.
⁴⁷ Universitat Pompeu Fabra, Barcelona, Spain.
⁴⁸ Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
⁴⁹ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
⁵⁰ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Centre for Mental Health, Würzburg, Germany.
⁵¹ Estonian Genome Center, University of Tartu, Tartu, Estonia.
⁵² Program in Medical and Population Genetics, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
⁵³ Genomics and Disease, Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Barcelona, Spain.
⁵⁴ Department of Psychiatry, University Hospital of Bellvitge -IDIBELL and CIBERobn, Barcelona, Spain.
⁵⁵ Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain.
⁵⁶ Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University (LMU), Munich, Germany.
⁵⁷ Schön Klinik Roseneck affiliated with the Medical Faculty of the University of Munich (LMU), Munich, Germany.
⁵⁸ Department of Cancer, Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
⁵⁹ Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
⁶⁰ Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
⁶¹ Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
⁶² Department of Biomedicine, University of Basel, Basel, Switzerland.
⁶³ Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁶⁴ Department of Psychiatry, Psychotherapy and Psychosomatics, Martin Luther University of Halle-Wittenberg, Halle, Germany.
⁶⁵ First Psychiatric Department, National and Kapodistrian University of Athens, Medical School, Eginition Hospital, Athens, Greece.
⁶⁶ CMME, Hôpital Sainte-Anne (GHU Paris Psychiatrie et Neurosciences), Paris Descartes University, Paris, France.
⁶⁷ Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁶⁸ Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁶⁹ Institute of Translational Genomics, Helmholtz Zentrum München, Neuherberg, Germany.
⁷⁰ Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
⁷¹ Zorg op Orde, Leidschendam, the Netherlands.
⁷² Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg University, Heidelberg, Germany.
⁷³ Department of Psychiatry, and Genetics and Genomics Sciences, Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁷⁴ Biological Psychiatry Laboratory, McLean Hospital/Harvard Medical School, Boston, MA, USA.
⁷⁵ Eating Disorders Unit, Parklandklinik, Bad Wildungen, Germany.
⁷⁶ Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, School of Medicine, Tokai University, Isehara, Japan.
⁷⁷ Faculty of Health Sciences, Palacky University, Olomouc, Czech Republic.
⁷⁸ Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
⁷⁹ Department of Psychiatry, First Faculty of Medicine, Charles University, Prague, Czech Republic.
⁸⁰ Department of Public Health, University of Helsinki, Helsinki, Finland.
⁸¹ Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
⁸² Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
⁸³ Eating Disorders Unit, Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria.
⁸⁴ Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, the Netherlands.
⁸⁵ Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
⁸⁶ Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
⁸⁷ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
⁸⁸ Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
⁸⁹ Department of Psychiatry, Seoul Paik Hospital, Inje University, Seoul, Korea.
⁹⁰ Rheumatology Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
⁹¹ Department of Psychology, Michigan State University, East Lansing, MI, USA.
⁹² Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.
⁹³ Department of Clinical Science, K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), University of Bergen, Bergen, Norway.
⁹⁴ Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
⁹⁵ Department of Clinical Medicine, Laboratory Building, Haukeland University Hospital, Bergen, Norway.
⁹⁶ American School of Professional Psychology, Argosy University, Northern Virginia, Arlington, VA, USA.
⁹⁷ Department of Cancer Epidemiology and Prevention, M Skłodowska-Curie Cancer Center - Oncology Center, Warsaw, Poland.
⁹⁸ BESE Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
⁹⁹ Department of Psychiatry, University of Lausanne-University Hospital of Lausanne (UNIL-CHUV), Lausanne, Switzerland.
¹⁰⁰ Department of Psychiatry, University of Campania "Luigi Vanvitelli", Naples, Italy.
¹⁰¹ Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
¹⁰² Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
¹⁰³ Department of Psychiatry, University College Cork, Cork, Ireland.
¹⁰⁴ HSE National Clinical Programme for Eating Disorders, Cork, Ireland.
¹⁰⁵ Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
¹⁰⁶ Department of Biomedical Data Science, Leiden University Medical Centre, Leiden, the Netherlands.
¹⁰⁷ Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
¹⁰⁸ Division of Child and Adolescent Psychiatry, Geneva University Hospital, Geneva, Switzerland.
¹⁰⁹ Great Ormond Street Institute of Child Health, University College London, London, UK.
¹¹⁰ National Center for PTSD, VA Boston Healthcare System, Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
¹¹¹ Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Italy.
¹¹² Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
¹¹³ Kartini Clinic, Portland, OR, USA.
¹¹⁴ Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
¹¹⁵ Center for Human Genome Research at the Massachusetts General Hospital, Boston, MA, USA.
¹¹⁶ Saint Joan de Déu Research Institute, Saint Joan de Déu Barcelona Children's Hospital, Barcelona, Spain.
¹¹⁷ Institute of Biomedicine (IBUB), University of Barcelona, Barcelona, Spain.
¹¹⁸ Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain.
¹¹⁹ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹²⁰ Department of Health Science, University of Florence, Florence, Italy.
¹²¹ Institute for Molecular Medicine Finland (FIMM), HiLIFE Unit, University of Helsinki, Helsinki, Finland.
¹²² Eating Disorders Research and Treatment Center, Department of Child and Adolescent Psychiatry, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
¹²³ Department of Psychological Medicine, University of Otago, Christchurch, New Zealand.
¹²⁴ Faculty of Medicine & Health Sciences, University of Aukland, Aukland, New Zealand.
¹²⁵ Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnologies, University of Pisa, Pisa, Italy.
¹²⁶ Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
¹²⁷ Department of Neurosciences, Padua Neuroscience Center, University of Padova, Padova, Italy.
¹²⁸ Institute of Medical Statistics, Computer and Data Sciences, Jena University Hospital, Jena, Germany.
¹²⁹ Department of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
¹³⁰ Institute of Psychiatry, Psychology and Neuroscience, Department of Psychological Medicine, King's College London, London, UK.
¹³¹ J. Craig Venter Institute (JCVI), La Jolla, CA, USA.
¹³² Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
¹³³ Department of Pediatrics and Center of Applied Genomics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
¹³⁴ Center for Eating Disorders Ursula, Rivierduinen, Leiden, the Netherlands.
¹³⁵ Department of Psychiatry, Leiden University Medical Centre, Leiden, the Netherlands.
¹³⁶ Department of Child and Adolescent Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
¹³⁷ IRCSS Fondazione Don Carlo Gnocchi, Florence, Italy.
¹³⁸ Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland.
¹³⁹ Department of Psychiatry, University of Naples SUN, Naples, Italy.
¹⁴⁰ Department of Psychiatry, University of Perugia, Perugia, Italy.
¹⁴¹ Brain Sciences Department, Stremble Ventures, Limassol, Cyprus.
¹⁴² Adolescent Health Unit, Second Department of Pediatrics, "P. & A. Kyriakou" Children's Hospital, University of Athens, Athens, Greece.
¹⁴³ Pediatric Intensive Care Unit, "P. & A. Kyriakou" Children's Hospital, University of Athens, Athens, Greece.
¹⁴⁴ Faculty of Social and Behavioral Sciences, Utrecht University, Utrecht, the Netherlands.
¹⁴⁵ Department of Internal Medicine VI, Psychosomatic Medicine and Psychotherapy, University Medical Hospital Tuebingen, Tuebingen, Germany.
¹⁴⁶ BioRealm, LLC, Walnut, CA, USA.
¹⁴⁷ Oregon Research Institute, Eugene, OR, USA.
¹⁴⁸ Christchurch Health and Development Study, University of Otago, Christchurch, New Zealand.
¹⁴⁹ The Center for Eating Disorders at Sheppard Pratt, Baltimore, MD, USA.
¹⁵⁰ Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA.
¹⁵¹ Eating Recovery Center, Denver, CO, USA.
¹⁵² Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
¹⁵³ Department of Psychiatry and Behavioral Science, University of North Dakota School of Medicine and Health Sciences, Fargo, ND, USA.
¹⁵⁴ Biostatistics and Computational Biology Unit, University of Otago, Christchurch, New Zealand.
¹⁵⁵ Department of Psychiatry and Biobehavioral Science, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
¹⁵⁶ David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
¹⁵⁷ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹⁵⁸ Centre for Mental Health, University Health Network, Toronto, Ontario, Canada.
¹⁵⁹ Program for Eating Disorders, University Health Network, Toronto, Ontario, Canada.
¹⁶⁰ Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹⁶¹ The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark.
¹⁶² Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
¹⁶³ Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.
¹⁶⁴ Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
¹⁶⁵ National Centre for Register-Based Research, Aarhus BSS, Aarhus University, Aarhus, Denmark.
¹⁶⁶ Centre for Integrated Register-based Research (CIRRAU), Aarhus University, Aarhus, Denmark.
¹⁶⁷ Canterbury District Health Board, Christchurch, New Zealand.
¹⁶⁸ Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.
¹⁶⁹ Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
¹⁷⁰ School of Psychology, Flinders University, Adelaide, South Australia, Australia.
¹⁷¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
¹⁷² Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. cynthia_bulik@med.unc.edu.
¹⁷³ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. cynthia_bulik@med.unc.edu.
¹⁷⁴ Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. cynthia_bulik@med.unc.edu.

PMID: 31308545
PMCID: PMC6779477
DOI: 10.1038/s41588-019-0439-2

Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Hunna J Watson et al. Nat Genet. 2019 Aug.

. 2019 Aug;51(8):1207-1214.

doi: 10.1038/s41588-019-0439-2. Epub 2019 Jul 15.

Authors

Affiliations

¹ Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
² School of Psychology, Curtin University, Perth, Western Australia, Australia.
³ School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia.
⁴ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵ Institute of Psychiatry, Psychology and Neuroscience, Social, Genetic and Developmental Psychiatry (SGDP) Centre, King's College London, London, UK.
⁶ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁷ National Institute for Health Research Biomedical Research Centre, King's College London and South London and Maudsley National Health Service Foundation Trust, London, UK.
⁸ Department of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
⁹ Department of Biomedicine, Aarhus University, Aarhus, Denmark.
¹⁰ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
¹¹ Center for Psychiatry Research, Stockholm Health Care Services, Stockholm City Council, Stockholm, Sweden.
¹² Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
¹³ QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
¹⁴ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
¹⁵ Stanley Center for Psychiatric Research, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
¹⁶ Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany.
¹⁷ Department of Medical and Molecular Genetics, King's College London, Guy's Hospital, London, UK.
¹⁸ Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
¹⁹ Center for Eating Disorders Rintveld, Altrecht Mental Health Institute, Zeist, the Netherlands.
²⁰ Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
²¹ Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
²² Department of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.
²³ NORMENT KG Jebsen Centre, Division of Mental Health and Addiction, University of Oslo, Oslo University Hospital, Oslo, Norway.
²⁴ Department of Psychiatry, Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
²⁵ Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
²⁶ INSERM 1266, Institute of Psychiatry and Neuroscience of Paris, Paris, France.
²⁷ Wellcome Sanger Institute, Hinxton, UK.
²⁸ Department of Medical Biology, School of Medicine, University of Split, Split, Croatia.
²⁹ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen University, Aachen, Germany.
³⁰ Department of Child and Adolescent Psychiatry, Klinikum Frankfurt/Oder, Frankfurt, Germany.
³¹ Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy.
³² Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
³³ Life Sciences Institute and Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
³⁴ Department of Emergency Psychiatry and Post-Acute Care, CHRU Montpellier, University of Montpellier, Montpellier, France.
³⁵ Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
³⁶ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
³⁷ School of Social and Community Medicine, University of Bristol, Bristol, UK.
³⁸ Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Hannover, Germany.
³⁹ Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
⁴⁰ Department of Neurosciences, University of Padova, Padova, Italy.
⁴¹ College of Nursing, Seattle University, Seattle, WA, USA.
⁴² Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA.
⁴³ Department of Psychiatry, Athens University Medical School, Athens University, Athens, Greece.
⁴⁴ L'institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France.
⁴⁵ Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland.
⁴⁶ Barcelona Institute of Science and Technology, Barcelona, Spain.
⁴⁷ Universitat Pompeu Fabra, Barcelona, Spain.
⁴⁸ Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
⁴⁹ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
⁵⁰ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Centre for Mental Health, Würzburg, Germany.
⁵¹ Estonian Genome Center, University of Tartu, Tartu, Estonia.
⁵² Program in Medical and Population Genetics, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
⁵³ Genomics and Disease, Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Barcelona, Spain.
⁵⁴ Department of Psychiatry, University Hospital of Bellvitge -IDIBELL and CIBERobn, Barcelona, Spain.
⁵⁵ Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain.
⁵⁶ Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University (LMU), Munich, Germany.
⁵⁷ Schön Klinik Roseneck affiliated with the Medical Faculty of the University of Munich (LMU), Munich, Germany.
⁵⁸ Department of Cancer, Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
⁵⁹ Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
⁶⁰ Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
⁶¹ Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
⁶² Department of Biomedicine, University of Basel, Basel, Switzerland.
⁶³ Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁶⁴ Department of Psychiatry, Psychotherapy and Psychosomatics, Martin Luther University of Halle-Wittenberg, Halle, Germany.
⁶⁵ First Psychiatric Department, National and Kapodistrian University of Athens, Medical School, Eginition Hospital, Athens, Greece.
⁶⁶ CMME, Hôpital Sainte-Anne (GHU Paris Psychiatrie et Neurosciences), Paris Descartes University, Paris, France.
⁶⁷ Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁶⁸ Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁶⁹ Institute of Translational Genomics, Helmholtz Zentrum München, Neuherberg, Germany.
⁷⁰ Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
⁷¹ Zorg op Orde, Leidschendam, the Netherlands.
⁷² Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg University, Heidelberg, Germany.
⁷³ Department of Psychiatry, and Genetics and Genomics Sciences, Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁷⁴ Biological Psychiatry Laboratory, McLean Hospital/Harvard Medical School, Boston, MA, USA.
⁷⁵ Eating Disorders Unit, Parklandklinik, Bad Wildungen, Germany.
⁷⁶ Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, School of Medicine, Tokai University, Isehara, Japan.
⁷⁷ Faculty of Health Sciences, Palacky University, Olomouc, Czech Republic.
⁷⁸ Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
⁷⁹ Department of Psychiatry, First Faculty of Medicine, Charles University, Prague, Czech Republic.
⁸⁰ Department of Public Health, University of Helsinki, Helsinki, Finland.
⁸¹ Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
⁸² Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
⁸³ Eating Disorders Unit, Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria.
⁸⁴ Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, the Netherlands.
⁸⁵ Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
⁸⁶ Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
⁸⁷ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
⁸⁸ Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
⁸⁹ Department of Psychiatry, Seoul Paik Hospital, Inje University, Seoul, Korea.
⁹⁰ Rheumatology Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
⁹¹ Department of Psychology, Michigan State University, East Lansing, MI, USA.
⁹² Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.
⁹³ Department of Clinical Science, K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), University of Bergen, Bergen, Norway.
⁹⁴ Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
⁹⁵ Department of Clinical Medicine, Laboratory Building, Haukeland University Hospital, Bergen, Norway.
⁹⁶ American School of Professional Psychology, Argosy University, Northern Virginia, Arlington, VA, USA.
⁹⁷ Department of Cancer Epidemiology and Prevention, M Skłodowska-Curie Cancer Center - Oncology Center, Warsaw, Poland.
⁹⁸ BESE Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
⁹⁹ Department of Psychiatry, University of Lausanne-University Hospital of Lausanne (UNIL-CHUV), Lausanne, Switzerland.
¹⁰⁰ Department of Psychiatry, University of Campania "Luigi Vanvitelli", Naples, Italy.
¹⁰¹ Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
¹⁰² Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
¹⁰³ Department of Psychiatry, University College Cork, Cork, Ireland.
¹⁰⁴ HSE National Clinical Programme for Eating Disorders, Cork, Ireland.
¹⁰⁵ Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
¹⁰⁶ Department of Biomedical Data Science, Leiden University Medical Centre, Leiden, the Netherlands.
¹⁰⁷ Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
¹⁰⁸ Division of Child and Adolescent Psychiatry, Geneva University Hospital, Geneva, Switzerland.
¹⁰⁹ Great Ormond Street Institute of Child Health, University College London, London, UK.
¹¹⁰ National Center for PTSD, VA Boston Healthcare System, Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
¹¹¹ Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Italy.
¹¹² Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
¹¹³ Kartini Clinic, Portland, OR, USA.
¹¹⁴ Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
¹¹⁵ Center for Human Genome Research at the Massachusetts General Hospital, Boston, MA, USA.
¹¹⁶ Saint Joan de Déu Research Institute, Saint Joan de Déu Barcelona Children's Hospital, Barcelona, Spain.
¹¹⁷ Institute of Biomedicine (IBUB), University of Barcelona, Barcelona, Spain.
¹¹⁸ Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain.
¹¹⁹ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹²⁰ Department of Health Science, University of Florence, Florence, Italy.
¹²¹ Institute for Molecular Medicine Finland (FIMM), HiLIFE Unit, University of Helsinki, Helsinki, Finland.
¹²² Eating Disorders Research and Treatment Center, Department of Child and Adolescent Psychiatry, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
¹²³ Department of Psychological Medicine, University of Otago, Christchurch, New Zealand.
¹²⁴ Faculty of Medicine & Health Sciences, University of Aukland, Aukland, New Zealand.
¹²⁵ Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnologies, University of Pisa, Pisa, Italy.
¹²⁶ Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
¹²⁷ Department of Neurosciences, Padua Neuroscience Center, University of Padova, Padova, Italy.
¹²⁸ Institute of Medical Statistics, Computer and Data Sciences, Jena University Hospital, Jena, Germany.
¹²⁹ Department of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
¹³⁰ Institute of Psychiatry, Psychology and Neuroscience, Department of Psychological Medicine, King's College London, London, UK.
¹³¹ J. Craig Venter Institute (JCVI), La Jolla, CA, USA.
¹³² Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
¹³³ Department of Pediatrics and Center of Applied Genomics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
¹³⁴ Center for Eating Disorders Ursula, Rivierduinen, Leiden, the Netherlands.
¹³⁵ Department of Psychiatry, Leiden University Medical Centre, Leiden, the Netherlands.
¹³⁶ Department of Child and Adolescent Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
¹³⁷ IRCSS Fondazione Don Carlo Gnocchi, Florence, Italy.
¹³⁸ Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland.
¹³⁹ Department of Psychiatry, University of Naples SUN, Naples, Italy.
¹⁴⁰ Department of Psychiatry, University of Perugia, Perugia, Italy.
¹⁴¹ Brain Sciences Department, Stremble Ventures, Limassol, Cyprus.
¹⁴² Adolescent Health Unit, Second Department of Pediatrics, "P. & A. Kyriakou" Children's Hospital, University of Athens, Athens, Greece.
¹⁴³ Pediatric Intensive Care Unit, "P. & A. Kyriakou" Children's Hospital, University of Athens, Athens, Greece.
¹⁴⁴ Faculty of Social and Behavioral Sciences, Utrecht University, Utrecht, the Netherlands.
¹⁴⁵ Department of Internal Medicine VI, Psychosomatic Medicine and Psychotherapy, University Medical Hospital Tuebingen, Tuebingen, Germany.
¹⁴⁶ BioRealm, LLC, Walnut, CA, USA.
¹⁴⁷ Oregon Research Institute, Eugene, OR, USA.
¹⁴⁸ Christchurch Health and Development Study, University of Otago, Christchurch, New Zealand.
¹⁴⁹ The Center for Eating Disorders at Sheppard Pratt, Baltimore, MD, USA.
¹⁵⁰ Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA.
¹⁵¹ Eating Recovery Center, Denver, CO, USA.
¹⁵² Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
¹⁵³ Department of Psychiatry and Behavioral Science, University of North Dakota School of Medicine and Health Sciences, Fargo, ND, USA.
¹⁵⁴ Biostatistics and Computational Biology Unit, University of Otago, Christchurch, New Zealand.
¹⁵⁵ Department of Psychiatry and Biobehavioral Science, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
¹⁵⁶ David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
¹⁵⁷ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹⁵⁸ Centre for Mental Health, University Health Network, Toronto, Ontario, Canada.
¹⁵⁹ Program for Eating Disorders, University Health Network, Toronto, Ontario, Canada.
¹⁶⁰ Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹⁶¹ The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark.
¹⁶² Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
¹⁶³ Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.
¹⁶⁴ Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
¹⁶⁵ National Centre for Register-Based Research, Aarhus BSS, Aarhus University, Aarhus, Denmark.
¹⁶⁶ Centre for Integrated Register-based Research (CIRRAU), Aarhus University, Aarhus, Denmark.
¹⁶⁷ Canterbury District Health Board, Christchurch, New Zealand.
¹⁶⁸ Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.
¹⁶⁹ Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
¹⁷⁰ School of Psychology, Flinders University, Adelaide, South Australia, Australia.
¹⁷¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
¹⁷² Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. cynthia_bulik@med.unc.edu.
¹⁷³ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. cynthia_bulik@med.unc.edu.
¹⁷⁴ Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. cynthia_bulik@med.unc.edu.

PMID: 31308545
PMCID: PMC6779477
DOI: 10.1038/s41588-019-0439-2

Abstract

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 men^2-4, 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.

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Conflict of interest statement

Competing interests

The authors report the following potential competing interests. O.A.A. received a speaker’s honorarium from Lundbeck. G.B. received grant funding and consultancy fees in preclinical genetics from Eli Lilly, consultancy fees from Otsuka and has received honoraria from Illumina. C.M.B. is a grant recipient from Shire Pharmaceuticals and served on Shire Scientific Advisory Board; she receives author royalties from Pearson. D.D. served as a speaker and on advisory boards, and has received consultancy fees for participation in research from various pharmaceutical industry companies including: AstraZeneca, Boehringer, Bristol Myers Squibb, Eli Lilly, Genesis Pharma, GlaxoSmithKline, Janssen, Lundbeck, Organon, Sanofi, UniPharma, and Wyeth; he has received unrestricted grants from Lilly and AstraZeneca as director of the Sleep Research Unit of Eginition Hospital (National and Kapodistrian University of Athens, Greece). J.I.H. has received grant support from Shire and Sunovion, and has received consulting fees from DiaMentis, Shire, and Sunovion. A.S.K. is a member of the Shire Canadian BED Advisory Board and is on the steering committee for the Shire B/educated Educational Symposium: June 15-16, 2018. J.L.K. served as an unpaid member of the scientific advisory board of AssurexHealth Inc. M.L. declares that, over the past 36 months, he has received lecture honoraria from Lundbeck and served as scientific consultant for EPID Research Oy. No other equity ownership, profit-sharing agreements, royalties, or patent. P.F.S. is on the Lundbeck advisory committee and is a Lundbeck grant recipient; he has served on the scientific advisory board for Pfizer, has received a consultation fee from Element Genomics, and a speaker reimbursement fee from Roche. J.T. has received an honorarium for participation in an EAP meeting and has received royalties from several books from Routledge, Wiley, and Oxford University press. T.W. has acted as a lecturer and scientific advisor to H. Lundbeck A/S. All other authors have no conflicts of interest to disclose.

Figures

**Figure 1.. The Manhattan plot for the primary genome-wide association meta-analysis of anorexia nervosa with 33 case-control samples (16,992 cases and 55,525 controls of European descent).**
The −log₁₀(P) values for the association tests (two-tailed) are shown on the y-axis and the chromosomes are ordered on the x-axis. Eight genetic loci surpassed genome-wide significance (−log₁₀(P) > 7.3). The lead variant is indicated by a diamond and green circles show the variants in linkage-disequilibrium. The blue and red colors differentiate adjacent chromosomes.

**Figure. 2.. Bonferroni-significant genetic correlations (SNP-r_gs) and standard errors (error bars) between anorexia nervosa and other phenotypes as estimated by LD score regression.**
Only traits with significant P values following Bonferroni correction are shown. Correlations with 447 phenotypes were tested (Bonferroni-corrected significance threshold P > 1.11 × 10⁻⁴). Complete results are shown in Table S10. PGC = Psychiatric Genomics Consortium, UKB = UK Biobank, HOMA-IR = Homeostatic model assessment - insulin resistance.

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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

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