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

Anorexia Nervosa Genetics Initiative, 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 AndoOle 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, Anne Farmer, Sietske G Helder, Gursharan Kalsi, Peter McGuffin, Marion Roberts, Ulrike Schmidt, Janet Treasure, Gerome Breen

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Abstract

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness 1, 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 disorders 6, and outcomes are unacceptably poor 7. 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.

Original languageEnglish
Pages (from-to)1207–1214
Number of pages8
JournalNature Genetics
Volume51
Issue number8
Early online date15 Jul 2019
DOIs
Publication statusPublished - 31 Aug 2019

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