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Medline ® Abstract for Reference 7

of 'What's new in psychiatry'

7
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Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa.
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Duncan L, Yilmaz Z, Gaspar H, Walters R, Goldstein J, Anttila V, Bulik-Sullivan B, Ripke S, Eating Disorders Working Group of the Psychiatric Genomics Consortium, Thornton L, Hinney A, Daly M, Sullivan PF, Zeggini E, Breen G, Bulik CM
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Am J Psychiatry. 2017;174(9):850. Epub 2017 May 12.
 
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.
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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.
PMID