TY - JOUR

T1 - Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

AU - Watson, Hunna J

AU - Yilmaz, Zeynep

AU - Thornton, Laura M

AU - Hübel, Christopher

AU - Coleman, Jonathan R I

AU - Gaspar, Héléna A

AU - Bryois, Julien

AU - Hinney, Anke

AU - Leppä, Virpi M

AU - Mattheisen, Manuel

AU - Medland, Sarah E

AU - Ripke, Stephan

AU - Yao, Shuyang

AU - Giusti-Rodríguez, Paola

AU - Hanscombe, Ken B

AU - Purves, Kirstin L

AU - Adan, Roger A H

AU - Alfredsson, Lars

AU - Ando, Tetsuya

AU - Andreassen, Ole A

AU - Baker, Jessica H

AU - Berrettini, Wade H

AU - Boehm, Ilka

AU - Boni, Claudette

AU - Perica, Vesna Boraska

AU - Buehren, Katharina

AU - Burghardt, Roland

AU - Cassina, Matteo

AU - Cichon, Sven

AU - Clementi, Maurizio

AU - Cone, Roger D

AU - Courtet, Philippe

AU - Crow, Scott

AU - Crowley, James J

AU - Danner, Unna N

AU - Davis, Oliver S P

AU - de Zwaan, Martina

AU - Dedoussis, George

AU - Degortes, Daniela

AU - DeSocio, Janiece E

AU - Dick, Danielle M

AU - Dikeos, Dimitris

AU - Dina, Christian

AU - Dmitrzak-Weglarz, Monika

AU - Docampo, Elisa

AU - Duncan, Laramie E

AU - Egberts, Karin

AU - Ehrlich, Stefan

AU - Li, Dong

AU - Werge, Thomas

AU - Anorexia Nervosa Genetics Initiative

PY - 2019/8

Y1 - 2019/8

N2 - 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.

AB - 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.

U2 - 10.1038/s41588-019-0439-2

DO - 10.1038/s41588-019-0439-2

M3 - Letter

C2 - 31308545

VL - 51

SP - 1207

EP - 1214

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 8

ER -