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

2019; Nature Portfolio; Volume: 51; Issue: 8 Linguagem: Inglês

10.1038/s41588-019-0439-2

1546-1718

Hunna J. Watson, Zeynep Yılmaz, Laura M. Thornton, Christopher Hübel, Jonathan R. I. Coleman, Héléna A. Gaspar, Julien Bryois, Anke Hinney, Virpi 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 J. 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‐Węglarz, 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 Foretová, 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, Hákon Hákonarson, 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, Vladimí­r Janout, Susana Jiménez‐Múrcia, Antonio Julià, Gursharan Kalsi, Deborah Kaminská, Jaakko Kaprio, Leila Karhunen, Andreas Karwautz, Martien J. Kas, James L. Kennedy, Anna Keski‐Rahkonen, Kirsty Kiezebrink, Youl‐Ri Kim, Lars Klareskog, Kelly L. Klump, Gun Peggy Knudsen, Maria C. La Via, Stéphanie Le Hellard, Robert D. Levitan, Dong Li, Lisa Lilenfeld, Bochao Lin, Jolanta Lissowska, Jurjen J. 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 S. Mitchell, Alessio Maria Monteleone, Palmiero Monteleone, Melissa A. Munn‐Chernoff, Benedetta Nacmias, Marie Navratilova, Ιωάννα Ντάλλα, Julie K. O’Toole, Roel A. Ophoff, Leonid Padyukov, Aarno Palotie, Jacques Pantel, Hana Papežová, Dalila Pinto, Raquel Rabionet, Anu Raevuori, Nicolás 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 Šlachtová, P. Eline Slagboom, M Landt, Agnieszka Slopien, Sandro Sorbi, Beata Świątkowska, Jin P. Szatkiewicz, Ioanna Tachmazidou, Elena Tenconi, Alfonso Tortorella, Federica Tozzi, Janet Treasure, Άρτεμις Τσίτσικα, Marta Tyszkiewicz‐Nwafor, Konstantinos Tziouvas, Annemarie Elburg, Eric F. van Furth, Gudrun Wagner, Esther Walton, Elisabeth Widén, 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 D. Gordon, Jakob Grove, Anjali K. Henders, Anders Juréus, Katherine M. Kirk, Janne Tidselbak Larsen, Richard Parker, Liselotte Petersen, Jennifer Jordan, Martin A. Kennedy, Grant W. Montgomery, Tracey Wade, Andreas Birgegård, Paul Lichtenstein, Claes Norring, Mikael Landén, Nicholas G. Martin, Preben Bo Mortensen, Patrick F. Sullivan, Gerome Breen, Cynthia M. Bulik,

Nutrition, Genetics, and Disease

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. Genome-wide analyses identify eight independent loci associated with anorexia nervosa. Genetic correlations implicate both psychiatric and metabolic components in the etiology of this disorder, even after adjusting for the effects of common variants associated with body mass index.