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Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa

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  • Laramie Duncan, From the UNC Center of Excellence for Eating Disorders, Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, N.C.; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston; the Social, Genetic, and Developmental Psychiatry Research Centre and Biomedical Research Centre for Mental Health at King's College London and South London and Maudsley NHS Trust; and the Broad Institute of MIT and Harvard, Cambridge, Mass.
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  • Zeynep Yilmaz, From the UNC Center of Excellence for Eating Disorders, Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, N.C.; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston; the Social, Genetic, and Developmental Psychiatry Research Centre and Biomedical Research Centre for Mental Health at King's College London and South London and Maudsley NHS Trust; and the Broad Institute of MIT and Harvard, Cambridge, Mass.
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  • Helena Gaspar, From the UNC Center of Excellence for Eating Disorders, Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, N.C.; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston; the Social, Genetic, and Developmental Psychiatry Research Centre and Biomedical Research Centre for Mental Health at King's College London and South London and Maudsley NHS Trust; and the Broad Institute of MIT and Harvard, Cambridge, Mass.
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  • Raymond K Walters, From the UNC Center of Excellence for Eating Disorders, Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, N.C.; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston; the Social, Genetic, and Developmental Psychiatry Research Centre and Biomedical Research Centre for Mental Health at King's College London and South London and Maudsley NHS Trust; and the Broad Institute of MIT and Harvard, Cambridge, Mass.
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  • Jackie Goldstein, From the UNC Center of Excellence for Eating Disorders, Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, N.C.; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston; the Social, Genetic, and Developmental Psychiatry Research Centre and Biomedical Research Centre for Mental Health at King's College London and South London and Maudsley NHS Trust; and the Broad Institute of MIT and Harvard, Cambridge, Mass.
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  • Verneri Anttila, From the UNC Center of Excellence for Eating Disorders, Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, N.C.; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston; the Social, Genetic, and Developmental Psychiatry Research Centre and Biomedical Research Centre for Mental Health at King's College London and South London and Maudsley NHS Trust; and the Broad Institute of MIT and Harvard, Cambridge, Mass.
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  • Brendan K Bulik-Sullivan, From the UNC Center of Excellence for Eating Disorders, Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, N.C.; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston; the Social, Genetic, and Developmental Psychiatry Research Centre and Biomedical Research Centre for Mental Health at King's College London and South London and Maudsley NHS Trust; and the Broad Institute of MIT and Harvard, Cambridge, Mass.
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  • Stephan Ripke, From the UNC Center of Excellence for Eating Disorders, Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, N.C.; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston; the Social, Genetic, and Developmental Psychiatry Research Centre and Biomedical Research Centre for Mental Health at King's College London and South London and Maudsley NHS Trust; and the Broad Institute of MIT and Harvard, Cambridge, Mass.
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  • Laura M. Thornton, From the UNC Center of Excellence for Eating Disorders, Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, N.C.; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston; the Social, Genetic, and Developmental Psychiatry Research Centre and Biomedical Research Centre for Mental Health at King's College London and South London and Maudsley NHS Trust; and the Broad Institute of MIT and Harvard, Cambridge, Mass.
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  • Anke Hinney, From the UNC Center of Excellence for Eating Disorders, Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, N.C.; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston; the Social, Genetic, and Developmental Psychiatry Research Centre and Biomedical Research Centre for Mental Health at King's College London and South London and Maudsley NHS Trust; and the Broad Institute of MIT and Harvard, Cambridge, Mass.
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  • Mark Daly, From the UNC Center of Excellence for Eating Disorders, Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, N.C.; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston; the Social, Genetic, and Developmental Psychiatry Research Centre and Biomedical Research Centre for Mental Health at King's College London and South London and Maudsley NHS Trust; and the Broad Institute of MIT and Harvard, Cambridge, Mass.
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  • Patrick F Sullivan, From the UNC Center of Excellence for Eating Disorders, Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, N.C.; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston; the Social, Genetic, and Developmental Psychiatry Research Centre and Biomedical Research Centre for Mental Health at King's College London and South London and Maudsley NHS Trust; and the Broad Institute of MIT and Harvard, Cambridge, Mass.
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  • Eleftheria Zeggini, From the UNC Center of Excellence for Eating Disorders, Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, N.C.; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston; the Social, Genetic, and Developmental Psychiatry Research Centre and Biomedical Research Centre for Mental Health at King's College London and South London and Maudsley NHS Trust; and the Broad Institute of MIT and Harvard, Cambridge, Mass.
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  • Gerome Breen, From the UNC Center of Excellence for Eating Disorders, Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, N.C.; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston; the Social, Genetic, and Developmental Psychiatry Research Centre and Biomedical Research Centre for Mental Health at King's College London and South London and Maudsley NHS Trust; and the Broad Institute of MIT and Harvard, Cambridge, Mass.
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  • Cynthia M Bulik, From the UNC Center of Excellence for Eating Disorders, Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, N.C.; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston; the Social, Genetic, and Developmental Psychiatry Research Centre and Biomedical Research Centre for Mental Health at King's College London and South London and Maudsley NHS Trust; and the Broad Institute of MIT and Harvard, Cambridge, Mass.
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  • Eating Disorders Working Group of the Psychiatric Genomics Consortium
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  • Preben Bo Mortensen (Member of author collaboration)

OBJECTIVE: The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes.

METHOD: Following uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h(2)SNP]), partitioned heritability, and genetic correlations (rg) between anorexia nervosa and 159 other phenotypes.

RESULTS: Results were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h(2)SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes.

CONCLUSIONS: Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

Original languageEnglish
JournalAmerican Journal of Psychiatry
Volume174
Issue9
Pages (from-to)850-858
ISSN0002-953X
DOIs
Publication statusPublished - 12 May 2017

    Research areas

  • Journal Article

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