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

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 men^2-4, 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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Affiliated Institutions

• Harokopio University of Athens GR
• Harvard University US
• University Hospital Heidelberg DE
• University Hospital of Basel CH
• King's College London GB
• University of Padua IT
• Virginia Commonwealth University US
• Tokai University JP
• University of Toronto CA
• University of Pennsylvania US
• National Center of Neurology and Psychiatry JP
• Poznan University of Medical Sciences PL
• University of Oslo
• University of North Carolina at Chapel Hill US
• Technische Universität Dresden DE
• Université de Montpellier FR
• Centre for Addiction and Mental Health CA
• Institut d'Investigació Biomédica de Bellvitge ES
• University of Aberdeen GB
• Ludwig-Maximilians-Universität München DE
• Karolinska Institutet SE
• Michigan State University US
• Massachusetts General Hospital US
• Centre National de la Recherche Scientifique FR
• Altrecht GGZ NL
• Barcelona Institute for Science and Technology ES
• University of Duisburg-Essen DE
• University of Minnesota US
• Klinikum Frankfurt Höchst DE
• QIMR Berghofer Medical Research Institute AU
• Charles University CZ
• Guy's Hospital GB
• University of Helsinki FI
• University Medical Center Utrecht NL
• Norwegian Institute of Public Health
• Eginition Hospital GR
• Inje University Seoul Paik Hospital KR
• Seattle University US
• Institut de Psychiatrie et Neurosciences de Paris FR
• Universitätsklinikum Würzburg DE
• Werner-Wicker-Klinik DE
• Aarhus University DK
• Masaryk Memorial Cancer Institute CZ
• RWTH Aachen University DE
• University of Bristol GB
• Children's Hospital of Philadelphia US
• Oslo University Hospital
• Centro de Investigación Biomédica en Red ES
• Martin Luther University Halle-Wittenberg DE
• Medical University of Vienna AT
• Inserm FR
• Karolinska University Hospital SE
• Palacký University Olomouc CZ
• Stanford University US
• University of Eastern Finland FI
• Institut du Thorax FR
• Vall d'Hebron Institut de Recerca ES
• University of Michigan US
• McLean Hospital US
• MRC Epidemiology Unit GB
• Wellcome Sanger Institute GB
• National Institute of Mental Health JP
• University of Tartu EE
• University of Bergen
• National and Kapodistrian University of Athens GR
• Heidelberg University DE
• Medizinische Hochschule Hannover DE

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