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

Hunna Watson; Zeynep Yilmaz; Laura Thornton; Christopher Hübel; Jonathan Coleman; Héléna Gaspar; Julien Bryois; Anke Hinney; Virpi Leppä; Manuel Mattheisen; Sarah Medland; Stephan Ripke; Shuyang Yao; Paola Giusti-Rodríguez; Ken Hanscombe; Kirstin Purves; Roger Adan; Lars Alfredsson; Tetsuya Ando; Ole Andreassen; Jessica Baker; Wade Berrettini; Ilka Boehm; Claudette Boni; Vesna Boraska Perica; Katharina Buehren; Roland Burghardt; Matteo Cassina; Sven Cichon; Maurizio Clementi; Roger Cone; Philippe Courtet; Scott Crow; James Crowley; Unna Danner; Oliver Davis; Martina de Zwaan; George V. Dedoussis; Daniela Degortes; Janiece Desocio; Danielle Dick; Dimitris Dikeos; Christian Dina; Monika Dmitrzak-Weglarz; Elisa Docampo; Laramie Duncan; Karin Egberts; Stefan Ehrlich; Geòrgia Escaramís; Tonu Esko; Xavier Estivill; Anne E. Farmer; Angela Favaro; Fernando Fernández-Aranda; Manfred Fichter; Krista Fischer; Manuel Föcker; Lenka Foretova; Andreas Forstner; Monica Forzan; Christopher 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 Helder; Stefan Herms; Beate Herpertz-Dahlmann; Wolfgang Herzog; Laura Huckins; James E Hudson; Hartmut Imgart; Hidetoshi Inoko; Vladimir Janout; Susana Jiménez-Murcia; Antonio Julià; Gursharan Kalsi; Deborah Kaminská; Jaakko Kaprio; Leila Karhunen; Andreas Karwautz; Martien Kas; James L. Kennedy; Anna Keski-Rahkonen; Kirsty Kiezebrink; Youl-Ri Kim; Lars Klareskog; Kelly Klump; Gun Peggy S Knudsen; Maria La Via; Stephanie Le Hellard; Robert Levitan; Dong Li; Lisa Lilenfeld; Bochao Danae Lin; Jolanta Lissowska; Jurjen Luykx; Pierre J. Magistretti; Mario Maj; Katrin Männik; 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 Munn-Chernoff; Benedetta Nacmias; Marie Navratilova; Ioanna Ntalla; Julie 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; Andre Scherag; Stephen W. Scherer; Ulrike Schmidt; Nicholas J. Schork; Alexandra Schosser; Jochen Seitz; Lenka Slachtova; P Eline Slagboom; Margarita Slof-Op 'T Landt; Agnieszka Slopien; Sandro Sorbi; Beata Świątkowska; Jin Szatkiewicz; Ioanna Tachmazidou; Elena Tenconi; Alfonso Tortorella; Federica Tozzi; Janet Treasure; Artemis Tsitsika; Marta Tyszkiewicz-Nwafor; Konstantinos Tziouvas; Annemarie van Elburg; Eric van Furth; Gudrun Wagner; Esther Walton; Elisabeth Widen; Eleftheria Zeggini; Stephanie Zerwas; Stephan Zipfel; Andrew Bergen; Joseph Boden; Harry Brandt; Steven Crawford; Katherine Halmi; L John Horwood; Craig Johnson; Allan Kaplan; Walter Kaye; James E Mitchell; Catherine M Olsen; John C. Pearson; Nancy L. Pedersen; Michael Strober; Thomas Werge; David C Whiteman; D Blake Woodside; Garret Stuber; Scott Gordon; Jakob Grove; Anjali K. Henders; Anders Juréus; Katherine Kirk; Janne Larsen; Richard Parker; Liselotte Petersen; Jennifer Jordan; Martin Kennedy; Grant W. Montgomery; Tracey Wade; Andreas Birgegård; Paul Lichtenstein; Claes Norring; Mikael Landén; Nicholas G Martin; Preben Bo Mortensen; Patrick Sullivan; Gerome Breen; Cynthia Bulik; Gun Peggy S. Knudsen; Julie O’toole; P. Eline Slagboom; Margarita Slof-Op ‘t Landt; L. John Horwood; D. Blake Woodside

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 Watson, Zeynep Yilmaz, Laura Thornton, Christopher Hübel, Jonathan Coleman, Héléna Gaspar, Julien Bryois, Anke Hinney, Virpi Leppä, Manuel Mattheisen, …

Nature Genetics, Vol.51(8), pp.1207-1214

08/2019

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

PMCID: PMC6779477

PMID: 31308545

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 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.

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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 Watson - University of North Carolina at Chapel Hill
Zeynep Yilmaz - University of North Carolina [Chapel Hill]
Laura Thornton - University of North Carolina at Chapel Hill
Christopher Hübel - King's College London
Jonathan Coleman - University of North Carolina [Chapel Hill]
Héléna Gaspar - King's College London
Julien Bryois - Karolinska Institutet
Anke Hinney - University of Duisburg-Essen
Virpi Leppä - Karolinska Institutet
Manuel Mattheisen - Aarhus University
Sarah Medland - QIMR Berghofer Medical Research Institute
Stephan Ripke - Massachusetts General Hospital
Shuyang Yao - Karolinska Institutet
Paola Giusti-Rodríguez - University of North Carolina at Chapel Hill
Ken Hanscombe - King's College London
Kirstin Purves - King's College London
Roger Adan
Lars Alfredsson - Karolinska Institutet
Tetsuya Ando - National Institute of Mental Health
Ole Andreassen - Oslo University Hospital
Jessica Baker - University of North Carolina at Chapel Hill
Wade Berrettini - University of Pennsylvania
Ilka Boehm - TU Dresden
Claudette Boni - Institut de Psychiatrie et Neurosciences de Paris
Vesna Boraska Perica - Wellcome Sanger Institute
Katharina Buehren - RWTH Aachen University
Roland Burghardt - Klinikum Frankfurt Höchst
Matteo Cassina - University of Padua
Sven Cichon - University Hospital of Basel
Maurizio Clementi - University of Padua
Roger Cone - University of Michigan–Ann Arbor
Philippe Courtet - Université de Montpellier
Scott Crow - University of Minnesota
James Crowley - Karolinska Institutet
Unna Danner - Altrecht GGZ
Oliver Davis
Martina de Zwaan - Medizinische Hochschule Hannover
George V. Dedoussis - Harokopio University of Athens
Daniela Degortes - University of Padua
Janiece Desocio - Seattle University
Danielle Dick - Virginia Commonwealth University
Dimitris Dikeos - National and Kapodistrian University of Athens
Christian Dina - Inserm
Monika Dmitrzak-Weglarz - Poznan University of Medical Sciences
Elisa Docampo - Barcelona Institute for Science and Technology
Laramie Duncan - Stanford University
Karin Egberts - Universitätsklinikum Würzburg
Stefan Ehrlich - TU Dresden
Geòrgia Escaramís - Barcelona Institute for Science and Technology
Tonu Esko - University of Tartu
Xavier Estivill - Barcelona Institute for Science and Technology
Anne E. Farmer - King's College London
Angela Favaro - University of Padua
Fernando Fernández-Aranda - Institut d'Investigació Biomédica de Bellvitge
Manfred Fichter - Ludwig-Maximilians-Universität München
Krista Fischer - University of Tartu
Manuel Föcker - University of Duisburg-Essen
Lenka Foretova - Masaryk Memorial Cancer Institute
Andreas Forstner - University Hospital of Basel
Monica Forzan - University of Padua
Christopher 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 - Institut de Psychiatrie et Neurosciences de Paris
Monica Gratacos Mayora - Barcelona Institute for Science and Technology
Sébastien Guillaume - Université de Montpellier
Yiran Guo - Children's Hospital of Philadelphia
Hakon Hakonarson - Children's Hospital of Philadelphia
Konstantinos Hatzikotoulas - Wellcome Sanger Institute
Joanna Hauser - Poznan University of Medical Sciences
Johannes Hebebrand - University of Duisburg-Essen
Sietske Helder - King's College London
Stefan Herms - University Hospital of Basel
Beate Herpertz-Dahlmann - RWTH Aachen University
Wolfgang Herzog - University Hospital Heidelberg
Laura Huckins - Wellcome Sanger Institute
James E Hudson
Hartmut Imgart - Werner-Wicker-Klinik
Hidetoshi Inoko - Tokai University
Vladimir Janout - Department of Optics [Univ Palacký]
Susana Jiménez-Murcia - Institut d'Investigació Biomédica de Bellvitge
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 Kas - University Medical Center Utrecht
James L. Kennedy - Centre for Addiction and Mental Health
Anna Keski-Rahkonen - University of Helsinki
Kirsty Kiezebrink - University of Aberdeen
Youl-Ri Kim
Lars Klareskog - Karolinska University Hospital
Kelly Klump - Michigan State University
Gun Peggy S Knudsen - Norwegian Institute of Public Health
Maria La Via - University of North Carolina at Chapel Hill
Stephanie Le Hellard - University of Bergen
Robert Levitan - Centre for Addiction and Mental Health
Dong Li - Children's Hospital of Philadelphia
Lisa Lilenfeld - Argosy University
Bochao Danae Lin - University Medical Center Utrecht
Jolanta Lissowska - The Maria Sklodowska-Curie National Research Institute of Oncology
Jurjen Luykx - University Medical Center Utrecht
Pierre J. Magistretti - King Abdullah University of Science and Technology
Mario Maj - University of Campania "Luigi Vanvitelli"
Katrin Männik - University of Tartu
Sara Marsal - Vall d'Hebron Institut de Recerca
Christian R. Marshall - Hospital for Sick Children
Morten Mattingsdal - University of Oslo
Sara Mcdevitt - University College Cork
Peter Mcguffin - King's College London
Andres Metspalu - University of Tartu
Ingrid Meulenbelt - Leiden University Medical Center
Nadia Micali - University of Geneva
Karen Mitchell - National Center for PTSD
Alessio Maria Monteleone - University of Campania "Luigi Vanvitelli"
Palmiero Monteleone - University of Salerno
Melissa Munn-Chernoff - University of North Carolina at Chapel Hill
Benedetta Nacmias - University of Florence
Marie Navratilova - Masaryk Memorial Cancer Institute
Ioanna Ntalla
Julie O'Toole
Roel A. Ophoff - University Medical Center Utrecht
Leonid Padyukov - Karolinska University Hospital
Aarno Palotie - Harvard University
Jacques Pantel - Inserm
Hana Papezova - Charles University
Dalila Pinto - Icahn School of Medicine at Mount Sinai
Raquel Rabionet - Hospital Sant Joan de Déu Barcelona
Anu Raevuori - University of Helsinki
Nicolas Ramoz - Institut de Psychiatrie et Neurosciences de Paris
Ted Reichborn-Kjennerud - Norwegian Institute of Public Health
Valdo Ricca - University of Florence
Samuli Ripatti - Broad Institute
Franziska Ritschel - TU Dresden
Marion Roberts - University of Otago
Alessandro Rotondo - University of Pisa
Dan Rujescu - Ludwig-Maximilians-Universität München
Filip Rybakowski - Poznan University of Medical Sciences
Paolo Santonastaso - University of Padua
Andre 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 Medical Center
Margarita Slof-Op 'T Landt
Agnieszka Slopien - Poznan University of Medical Sciences
Sandro Sorbi - University of Florence
Beata Świątkowska - Nofer Institute of Occupational Medicine
Jin Szatkiewicz - University of North Carolina at Chapel Hill
Ioanna Tachmazidou - Wellcome Sanger Institute
Elena Tenconi - University of Padua
Alfonso Tortorella - University of Naples Federico II
Federica Tozzi - Neurosciences Centre of Excellence in Drug Discovery
Janet Treasure - King's College London
Artemis Tsitsika
Marta Tyszkiewicz-Nwafor - Poznan University of Medical Sciences
Konstantinos Tziouvas - Panagiotis & Aglaia Kyriakou Children's Hospital
Annemarie van Elburg - Utrecht University
Eric van Furth - GGZ Rivierduinen
Gudrun Wagner - Medical University of Vienna
Esther Walton - TU Dresden
Elisabeth Widen - University of Helsinki
Eleftheria Zeggini - Helmholtz Zentrum München
Stephanie Zerwas - University of North Carolina at Chapel Hill
Stephan Zipfel
Andrew Bergen - BioRealm
Joseph Boden - University of Otago
Harry Brandt - Sheppard and Enoch Pratt Hospital
Steven Crawford - Sheppard and Enoch Pratt Hospital
Katherine Halmi - Cornell University
L John Horwood - University of Otago
Craig Johnson - The Recovery Center
Allan Kaplan - Centre for Addiction and Mental Health
Walter Kaye - University of California, San Diego
James E Mitchell - University of North Dakota
Catherine M Olsen - QIMR Berghofer Medical Research Institute
John C. Pearson - Department of Physics and Astronomy [Leicester]
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 - University of Toronto
Garret Stuber - University of North Carolina at Chapel Hill
Scott Gordon - QIMR Berghofer Medical Research Institute
Jakob Grove - Lundbeck Foundation
Anjali K. Henders - University of Queensland
Anders Juréus - Karolinska Institutet
Katherine Kirk - QIMR Berghofer Medical Research Institute
Janne Larsen - Lundbeck Foundation
Richard Parker - QIMR Berghofer Medical Research Institute
Liselotte Petersen - Lundbeck Foundation
Jennifer Jordan - University of Otago
Martin Kennedy - University of Otago
Grant W. Montgomery - University of Queensland
Tracey Wade - Flinders University
Andreas Birgegård - Stockholm County Council
Paul Lichtenstein - Karolinska Institutet
Claes Norring - Stockholm County Council
Mikael Landén - University of Gothenburg
Nicholas G Martin - QIMR Berghofer Medical Research Institute
Preben Bo Mortensen - Lundbeck Foundation
Patrick Sullivan - Karolinska Institutet
Gerome Breen - South London and Maudsley NHS Foundation Trust
Cynthia Bulik - University of North Carolina at Chapel Hill
Gun Peggy S. Knudsen - Norwegian Institute of Public Health
Julie O’toole - Oregon Clinic
P. Eline Slagboom - Leiden University Medical Center
Margarita Slof-Op ‘t Landt
L. John Horwood - University of Otago
D. Blake Woodside - University of Toronto
Publication Details: Nature Genetics, Vol.51(8), pp.1207-1214
Identifiers: 9938191709311
Academic Unit: Institut de Génomique Fonctionnelle - IGF
Language: English
Resource Type: Journal article
Local Fields: hal-02573041