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

Hunna Watson Zeynep Yilmaz 1 Laura Thornton 1 Christopher Hübel 1 Jonathan Coleman 1 Héléna Gaspar Julien Bryois Anke Hinney Virpi Leppä Manuel Mattheisen Sarah Medland Stephan Ripke Shuyang Yao Paola Giusti-Rodríguez 1 Ken Hanscombe Kirstin Purves Roger Adan Lars Alfredsson Tetsuya Ando Ole Andreassen 2 Jessica Baker Wade Berrettini 3 Ilka Boehm Claudette Boni 4 Vesna Boraska Perica Katharina Buehren Roland Burghardt Matteo Cassina Sven Cichon Maurizio Clementi 5 Roger Cone Philippe Courtet 6, 7 Scott Crow James Crowley 1 Unna Danner Oliver Davis Martina de Zwaan George Dedoussis 8 Daniela Degortes Janiece Desocio Danielle Dick Dimitris Dikeos 8 Christian Dina 9 Monika Dmitrzak-Weglarz Elisa Docampo Laramie Duncan Karin Egberts Stefan Ehrlich Geòrgia Escaramís Tonu Esko Xavier Estivill 10 Anne Farmer 11 Angela Favaro Fernando Fernández-Aranda 12 Manfred Fichter Krista Fischer Manuel Föcker Lenka Foretova 13 Andreas Forstner 14 Monica Forzan Christopher Franklin Steven Gallinger Ina Giegling Johanna Giuranna Fragiskos Gonidakis 15 Philip Gorwood 4 Monica Gratacos Mayora Sébastien Guillaume 7, 6 Yiran Guo Hakon Hakonarson 16 Konstantinos Hatzikotoulas Joanna Hauser Johannes Hebebrand 17 Sietske Helder Stefan Herms Beate Herpertz-Dahlmann 18 Wolfgang Herzog Laura Huckins 19 James Hudson Hartmut Imgart Hidetoshi Inoko 20 Vladimir Janout 21 Susana Jiménez-Murcia 12 Antonio Julià 22 Gursharan Kalsi Deborah Kaminská Jaakko Kaprio 23 Leila Karhunen Andreas Karwautz 24 Martien Kas James Kennedy Anna Keski-Rahkonen 25 Kirsty Kiezebrink Youl-Ri Kim Lars Klareskog 26 Kelly Klump Gun Peggy S Knudsen Maria La Via Stephanie Le Hellard 27 Robert Levitan Dong Li Lisa Lilenfeld Bochao Danae Lin Jolanta Lissowska 28 Jurjen Luykx Pierre Magistretti Mario Maj 29 Katrin Männik 30 Sara Marsal Christian Marshall 31 Morten Mattingsdal 2 Sara Mcdevitt Peter Mcguffin 11 Andres Metspalu 32 Ingrid Meulenbelt 33 Nadia Micali 34 Karen Mitchell Alessio Maria Monteleone Palmiero Monteleone 35 Melissa Munn-Chernoff Benedetta Nacmias 36 Marie Navratilova 37 Ioanna Ntalla Julie O'Toole Roel Ophoff 38 Leonid Padyukov 39 Aarno Palotie 40 Jacques Pantel 41, 42 Hana Papezova 43 Dalila Pinto 31 Raquel Rabionet 10 Anu Raevuori 25 Nicolas Ramoz 4 Ted Reichborn-Kjennerud 44 Valdo Ricca Samuli Ripatti 45 Franziska Ritschel Marion Roberts Alessandro Rotondo Dan Rujescu 46 Filip Rybakowski Paolo Santonastaso Andre Scherag 47 Stephen Scherer 31 Ulrike Schmidt Nicholas Schork 48 Alexandra Schosser 49 Jochen Seitz Lenka Slachtova P Eline Slagboom 50 Margarita Slof-Op 'T Landt Agnieszka Slopien Sandro Sorbi 36 Beata Świątkowska Jin Szatkiewicz 51 Ioanna Tachmazidou Elena Tenconi Alfonso Tortorella 52 Federica Tozzi 53 Janet Treasure Artemis Tsitsika Marta Tyszkiewicz-Nwafor Konstantinos Tziouvas Annemarie van Elburg 54 Eric van Furth Gudrun Wagner Esther Walton Elisabeth Widen 46 Eleftheria Zeggini 55 Stephanie Zerwas Stephan Zipfel Andrew Bergen 56 Joseph Boden Harry Brandt Steven Crawford Katherine Halmi 57 L John Horwood Craig Johnson 58 Allan Kaplan Walter Kaye 59 James E Mitchell Catherine Olsen 60 John Pearson 61 Nancy Pedersen 45 Michael Strober 62 Thomas Werge 63 David Whiteman 60 D Blake Woodside Garret Stuber Scott Gordon Jakob Grove 64 Anjali Henders 65 Anders Juréus Katherine Kirk Janne Larsen Richard Parker 66 Liselotte Petersen 67 Jennifer Jordan Martin Kennedy 68 Grant Montgomery 46 Tracey Wade Andreas Birgegård Paul Lichtenstein 39 Claes Norring Mikael Landén 69 Nicholas Martin 70 Preben Bo Mortensen 71 Patrick Sullivan 46 Gerome Breen 11 Cynthia Bulik 1 Gun Peggy S. Knudsen Julie O’toole P. Eline Slagboom 72 Margarita Slof-Op ‘t Landt L. John Horwood D. Blake Woodside
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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https://hal.umontpellier.fr/hal-02573041
Contributeur : Cécile Nowak <>
Soumis le : jeudi 14 mai 2020 - 09:30:25
Dernière modification le : mercredi 27 mai 2020 - 04:08:44

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Hunna Watson, Zeynep Yilmaz, Laura Thornton, Christopher Hübel, Jonathan Coleman, et al.. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nature Genetics, Nature Publishing Group, 2019, 51 (8), pp.1207-1214. ⟨10.1038/s41588-019-0439-2⟩. ⟨hal-02573041⟩

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