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

Hunna J Watson; Zeynep Yilmaz; Laura M Thornton; Christopher Hübel; Jonathan R I Coleman; Héléna A Gaspar; Julien Bryois; Anke Hinney; Virpi M Leppä; Manuel Mattheisen; Sarah E Medland; Stephan Ripke; Shuyang Yao; Paola Giusti-Rodríguez; Ken B Hanscombe; Kirstin L Purves; Roger A H Adan; Lars Alfredsson; Tetsuya Ando; Ole A Andreassen; Jessica H Baker; Wade H Berrettini; Ilka Boehm; Claudette Boni; Vesna Boraska Perica; Katharina Buehren; Roland Burghardt; Matteo Cassina; Sven Cichon; Maurizio Clementi; Roger D Cone; Philippe Courtet; Scott Crow; James J Crowley; Unna N Danner; Oliver S P Davis; Martina de Zwaan; George Dedoussis; Daniela Degortes; Janiece E DeSocio; Danielle M Dick; Dimitris Dikeos; Christian Dina; Monika Dmitrzak-Weglarz; Elisa Docampo; Laramie E Duncan; Karin Egberts; Stefan Ehrlich; Geòrgia Escaramís; Tõnu Esko; Xavier Estivill; Anne Farmer; Angela Favaro; Fernando Fernández-Aranda; Manfred M Fichter; Krista Fischer; Manuel Föcker; Lenka Foretova; Andreas J Forstner; Monica Forzan; Christopher S Franklin; Steven Gallinger; Ina Giegling; Johanna Giuranna; Fragiskos Gonidakis; Philip Gorwood; Monica Gratacos Mayora; Sébastien Guillaume; Yiran Guo; Hakon Hakonarson; Konstantinos Hatzikotoulas; Joanna Hauser; Johannes Hebebrand; Sietske G Helder; Stefan Herms; Beate Herpertz-Dahlmann; Wolfgang Herzog; Laura M Huckins; James I Hudson; Hartmut Imgart; Hidetoshi Inoko; Vladimir Janout; Susana Jiménez-Murcia; Antonio Julià; Gursharan Kalsi; Deborah Kaminská; Jaakko Kaprio; Leila Karhunen; Andreas Karwautz; Martien J H Kas; James L Kennedy; Anna Keski-Rahkonen; Kirsty Kiezebrink; Youl-Ri Kim; Lars Klareskog; Kelly L Klump; Gun Peggy S Knudsen; Maria C La Via; Stephanie Le Hellard; Robert D Levitan; Dong Li; Lisa Lilenfeld; Bochao Danae Lin; Jolanta Lissowska; Jurjen Luykx; Pierre J Magistretti; Mario Maj; Katrin Mannik; Sara Marsal; Christian R Marshall; Morten Mattingsdal; Sara McDevitt; Peter McGuffin; Andres Metspalu; Ingrid Meulenbelt; Nadia Micali; Karen Mitchell; Alessio Maria Monteleone; Palmiero Monteleone; Melissa A Munn-Chernoff; Benedetta Nacmias; Marie Navratilova; Ioanna Ntalla; Julie K O'Toole; Roel A Ophoff; Leonid Padyukov; Aarno Palotie; Jacques Pantel; Hana Papezova; Dalila Pinto; Raquel Rabionet; Anu Raevuori; Nicolas Ramoz; Ted Reichborn-Kjennerud; Valdo Ricca; Samuli Ripatti; Franziska Ritschel; Marion Roberts; Alessandro Rotondo; Dan Rujescu; Filip Rybakowski; Paolo Santonastaso; André Scherag; Stephen W Scherer; Ulrike Schmidt; Nicholas J Schork; Alexandra Schosser; Jochen Seitz; Lenka Slachtova; P Eline Slagboom; Margarita C T Slof-Op 't Landt; Agnieszka Slopien; Sandro Sorbi; Beata Świątkowska; Jin P Szatkiewicz; Ioanna Tachmazidou; Elena Tenconi; Alfonso Tortorella; Federica Tozzi; Janet Treasure; Artemis Tsitsika; Marta Tyszkiewicz-Nwafor; Konstantinos Tziouvas; Annemarie A van Elburg; Eric F van Furth; Gudrun Wagner; Esther Walton; Elisabeth Widen; Eleftheria Zeggini; Stephanie Zerwas; Stephan Zipfel; Andrew W Bergen; Joseph M Boden; Harry Brandt; Steven Crawford; Katherine A Halmi; L John Horwood; Craig Johnson; Allan S Kaplan; Walter H Kaye; James E Mitchell; Catherine M Olsen; John F Pearson; Nancy L Pedersen; Michael Strober; Thomas Werge; David C Whiteman; D Blake Woodside; Garret D Stuber; Scott Gordon; Jakob Grove; Anjali K Henders; Anders Juréus; Katherine M Kirk; Janne T Larsen; Richard Parker; Liselotte Petersen; Jennifer Jordan; Martin Kennedy; Grant W Montgomery; Tracey D Wade; Andreas Birgegård; Paul Lichtenstein; Claes Norring; Mikael Landén; Nicholas G Martin; Preben Bo Mortensen; Patrick F Sullivan; Gerome Breen; Cynthia M Bulik; Anorexia Nervosa Genetics Initiative

doi:10.1038/s41588-019-0439-2

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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

Hunna J Watson, Zeynep Yilmaz, Laura M Thornton, Christopher Hübel, Jonathan R I Coleman, Héléna A Gaspar, Julien Bryois, Anke Hinney, Virpi M Leppä, Manuel Mattheisen, …

Nature genetics, Vol.51(8), pp.1207-+

01/08/2019

DOI: https://doi.org/10.1038/s41588-019-0439-2

PMCID: PMC6779477

PMID: 31308545

Abstract

Adult

Anorexia Nervosa - etiology

Anorexia Nervosa - genetics

Anorexia Nervosa - pathology

Body Mass Index

Case-Control Studies

Female

Genetic Predisposition to Disease

Genome-Wide Association Study

Genomics - methods

Humans

Male

Mental Disorders - complications

Mental Disorders - genetics

Metabolic Diseases - complications

Metabolic Diseases - genetics

Phenotype

Prognosis

Quantitative Trait Loci

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness , affecting 0.9-4% of women and 0.3% of men , with twin-based heritability estimates of 50-60% . Mortality rates are higher than those in other psychiatric disorders , and outcomes are unacceptably poor . Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI) 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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Title: Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa
Creators - without role: Hunna J Watson - University of Western Australia
Zeynep Yilmaz - University of North Carolina at Chapel Hill
Laura M Thornton - University of North Carolina at Chapel Hill
Christopher Hübel - Karolinska Institutet
Jonathan R I Coleman - King's College London
Héléna A Gaspar - King's College London
Julien Bryois - Karolinska Institutet
Anke Hinney - University of Duisburg-Essen
Virpi M Leppä - Karolinska Institutet
Manuel Mattheisen - University of Würzburg
Sarah E Medland - QIMR Berghofer Medical Research Institute
Stephan Ripke - Charité - Universitätsmedizin Berlin
Shuyang Yao - Karolinska Institutet
Paola Giusti-Rodríguez - University of North Carolina at Chapel Hill
Ken B Hanscombe - King's College London
Kirstin L Purves - King's College London
Roger A H Adan - University of Gothenburg
Lars Alfredsson - Karolinska Institutet
Tetsuya Ando - National Center of Neurology and Psychiatry
Ole A Andreassen - Oslo University Hospital
Jessica H Baker - University of North Carolina at Chapel Hill
Wade H Berrettini - University of Pennsylvania
Ilka Boehm - Faculty
Claudette Boni - Institute of Psychiatry and Neuroscience of Paris
Vesna Boraska Perica - University of Split
Katharina Buehren - RWTH Aachen University
Roland Burghardt - Department of Child and Adolescent Psychiatry, Klinikum Frankfurt/Oder, Frankfurt, Germany
Matteo Cassina - Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy
Sven Cichon - University Hospital of Basel
Maurizio Clementi - Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy
Roger D Cone - University of Michigan–Ann Arbor
Philippe Courtet - University of Montpellier
Scott Crow - University of Minnesota
James J Crowley - Karolinska Institutet
Unna N Danner - Center for Eating Disorders Rintveld, Altrecht Mental Health Institute, Zeist, the Netherlands
Oliver S P Davis - University of Bristol
Martina de Zwaan - Medizinische Hochschule Hannover
George Dedoussis - Harokopio University of Athens
Daniela Degortes - Department of Neurosciences, University of Padova, Padova, Italy
Janiece E DeSocio - Seattle University
Danielle M Dick - Virginia Commonwealth University
Dimitris Dikeos - National and Kapodistrian University of Athens
Christian Dina - Nantes Université
Monika Dmitrzak-Weglarz - Poznan University of Medical Sciences
Elisa Docampo - Centro de Investigación Biomédica en Red
Laramie E Duncan - Stanford University
Karin Egberts - Universitätsklinikum Würzburg
Stefan Ehrlich - Faculty
Geòrgia Escaramís - Centro de Investigación Biomédica en Red
Tõnu Esko - Harvard University
Xavier Estivill - Centre for Genomic Regulation
Anne Farmer - King's College London
Angela Favaro - Department of Neurosciences, University of Padova, Padova, Italy
Fernando Fernández-Aranda - Universitat de Barcelona
Manfred M Fichter - Schön Klinik Roseneck
Krista Fischer - University of Tartu
Manuel Föcker - University of Duisburg-Essen
Lenka Foretova - Masaryk Memorial Cancer Institute
Andreas J Forstner - University of Basel
Monica Forzan - Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy
Christopher S Franklin - Wellcome Sanger Institute
Steven Gallinger - University of Toronto
Ina Giegling - Martin Luther University Halle-Wittenberg
Johanna Giuranna - University of Duisburg-Essen
Fragiskos Gonidakis - National and Kapodistrian University of Athens
Philip Gorwood - Paris Descartes University
Monica Gratacos Mayora - Centro de Investigación Biomédica en Red
Sébastien Guillaume - University of Montpellier
Yiran Guo - Children's Hospital of Philadelphia
Hakon Hakonarson - University of Pennsylvania
Konstantinos Hatzikotoulas - Helmholtz Zentrum München
Joanna Hauser - Poznan University of Medical Sciences
Johannes Hebebrand - University of Duisburg-Essen
Sietske G Helder - Zorg op Orde, Leidschendam, the Netherlands
Stefan Herms - University of Basel
Beate Herpertz-Dahlmann - RWTH Aachen University
Wolfgang Herzog - University Hospital Heidelberg
Laura M Huckins - Icahn School of Medicine at Mount Sinai
James I Hudson - Biological Psychiatry Laboratory, McLean Hospital/Harvard Medical School, Boston, MA, USA
Hartmut Imgart - Eating Disorders Unit, Parklandklinik, Bad Wildungen, Germany
Hidetoshi Inoko - Tokai University
Vladimir Janout - Palacký University Olomouc
Susana Jiménez-Murcia - Universitat de Barcelona
Antonio Julià - Vall d'Hebron Institut de Recerca
Gursharan Kalsi - King's College London
Deborah Kaminská - Charles University
Jaakko Kaprio - University of Helsinki
Leila Karhunen - University of Eastern Finland
Andreas Karwautz - Medical University of Vienna
Martien J H Kas - University of Groningen
James L Kennedy - University of Toronto
Anna Keski-Rahkonen - University of Helsinki
Kirsty Kiezebrink - University of Aberdeen
Youl-Ri Kim - Inje University
Lars Klareskog - Karolinska University Hospital
Kelly L Klump - Michigan State University
Gun Peggy S Knudsen - Norwegian Institute of Public Health
Maria C La Via - University of North Carolina at Chapel Hill
Stephanie Le Hellard - Haukeland University Hospital
Robert D Levitan - University of Toronto
Dong Li - Children's Hospital of Philadelphia
Lisa Lilenfeld - University of Northern Virginia
Bochao Danae Lin - University Medical Center Utrecht
Jolanta Lissowska - Department of Cancer Epidemiology and Prevention, M Skłodowska-Curie Cancer Center - Oncology Center, Warsaw, Poland
Jurjen Luykx - University Medical Center Utrecht
Pierre J Magistretti - University Hospital of Lausanne
Mario Maj - University of Campania "Luigi Vanvitelli"
Katrin Mannik - University of Lausanne
Sara Marsal - Vall d'Hebron Institut de Recerca
Christian R Marshall - Hospital for Sick Children
Morten Mattingsdal - Oslo University Hospital
Sara McDevitt - HSE National Clinical Programme for Eating Disorders, Cork, Ireland
Peter McGuffin - King's College London
Andres Metspalu - University of Tartu
Ingrid Meulenbelt - Leiden University
Nadia Micali - UCL Australia
Karen Mitchell - Boston University School of Medicine
Alessio Maria Monteleone - University of Campania "Luigi Vanvitelli"
Palmiero Monteleone - University of Salerno
Melissa A Munn-Chernoff - University of North Carolina at Chapel Hill
Benedetta Nacmias - University of Florence
Marie Navratilova - Masaryk Memorial Cancer Institute
Ioanna Ntalla - Harokopio University of Athens
Julie K O'Toole - Kartini Clinic, Portland, OR, USA
Roel A Ophoff - University of California, Los Angeles
Leonid Padyukov - Karolinska University Hospital
Aarno Palotie - Massachusetts General Hospital
Jacques Pantel - Institute of Psychiatry and Neuroscience of Paris
Hana Papezova - Charles University
Dalila Pinto - Icahn School of Medicine at Mount Sinai
Raquel Rabionet - Universitat de Barcelona
Anu Raevuori - University of Helsinki
Nicolas Ramoz - Institute of Psychiatry and Neuroscience of Paris
Ted Reichborn-Kjennerud - University of Oslo
Valdo Ricca - University of Florence
Samuli Ripatti - University of Helsinki
Franziska Ritschel - Faculty
Marion Roberts - Faculty
Alessandro Rotondo - University of Pisa
Dan Rujescu - Martin Luther University Halle-Wittenberg
Filip Rybakowski - Poznan University of Medical Sciences
Paolo Santonastaso - Department of Neurosciences, Padua Neuroscience Center, University of Padova, Padova, Italy
André Scherag - Jena University Hospital
Stephen W Scherer - Hospital for Sick Children
Ulrike Schmidt - King's College London
Nicholas J Schork - J. Craig Venter Institute
Alexandra Schosser - Medical University of Vienna
Jochen Seitz - RWTH Aachen University
Lenka Slachtova - Charles University
P Eline Slagboom - Leiden University
Margarita C T Slof-Op 't Landt - Leiden University
Agnieszka Slopien - Poznan University of Medical Sciences
Sandro Sorbi - Florence
Beata Świątkowska - Nofer Institute of Occupational Medicine
Jin P Szatkiewicz - University of North Carolina at Chapel Hill
Ioanna Tachmazidou - Wellcome Sanger Institute
Elena Tenconi - Department of Neurosciences, University of Padova, Padova, Italy
Alfonso Tortorella - University of Perugia
Federica Tozzi - Brain Sciences Department, Stremble Ventures, Limassol, Cyprus
Janet Treasure - King's College London
Artemis Tsitsika - National and Kapodistrian University of Athens
Marta Tyszkiewicz-Nwafor - Poznan University of Medical Sciences
Konstantinos Tziouvas - National and Kapodistrian University of Athens
Annemarie A van Elburg - Utrecht University
Eric F van Furth - Leiden University
Gudrun Wagner - Medical University of Vienna
Esther Walton - Faculty
Elisabeth Widen - University of Helsinki
Eleftheria Zeggini - Helmholtz Zentrum München
Stephanie Zerwas - University of North Carolina at Chapel Hill
Stephan Zipfel - Department of Internal Medicine VI, Psychosomatic Medicine and Psychotherapy, University Medical Hospital Tuebingen, Tuebingen, Germany
Andrew W Bergen - Oregon Research Institute
Joseph M Boden - University of Otago
Harry Brandt - Sheppard and Enoch Pratt Hospital
Steven Crawford - Sheppard and Enoch Pratt Hospital
Katherine A Halmi - Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA
L John Horwood - University of Otago
Craig Johnson - The Recovery Center
Allan S Kaplan - University of Toronto
Walter H Kaye - University of California, San Diego
James E Mitchell - University of North Dakota
Catherine M Olsen - QIMR Berghofer Medical Research Institute
John F Pearson - University of Otago
Nancy L Pedersen - Karolinska Institutet
Michael Strober - University of California, Los Angeles
Thomas Werge - University of Copenhagen
David C Whiteman - QIMR Berghofer Medical Research Institute
D Blake Woodside - Program for Eating Disorders, University Health Network, Toronto, Ontario, Canada
Garret D Stuber - University of North Carolina at Chapel Hill
Scott Gordon - QIMR Berghofer Medical Research Institute
Jakob Grove - Aarhus University
Anjali K Henders - University of Queensland
Anders Juréus - Karolinska Institutet
Katherine M Kirk - QIMR Berghofer Medical Research Institute
Janne T Larsen - Aarhus University
Richard Parker - QIMR Berghofer Medical Research Institute
Liselotte Petersen - Aarhus University
Jennifer Jordan - Canterbury District Health Board
Martin Kennedy - University of Otago
Grant W Montgomery - University of Queensland
Tracey D Wade - Flinders University
Andreas Birgegård - Stockholm Health Care Services
Paul Lichtenstein - Karolinska Institutet
Claes Norring - Stockholm Health Care Services
Mikael Landén - University of Gothenburg
Nicholas G Martin - QIMR Berghofer Medical Research Institute
Preben Bo Mortensen - Aarhus University
Patrick F Sullivan - Karolinska Institutet
Gerome Breen - King's College London
Cynthia M Bulik - University of North Carolina at Chapel Hill
Anorexia Nervosa Genetics Initiative
Publication Details: Nature genetics, Vol.51(8), pp.1207-+
Grant note: K01 AA025113 / NIAAA NIH HHS U01 HG006830 / NHGRI NIH HHS R21 MH115397 / NIMH NIH HHS K01 MH109772 / NIMH NIH HHS R21 MH104831 / NIMH NIH HHS U01 MH109536 / NIMH NIH HHS U01 MH109528 / NIMH NIH HHS K01 MH109782 / NIMH NIH HHS R01 MH092793 / NIMH NIH HHS R01 MH106611 / NIMH NIH HHS K01 MH106675 / NIMH NIH HHS
Identifiers: 9941782908331
Academic Unit: King Abdullah University of Science & Technology
Language: English
Resource Type: Journal article