Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/120516
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Type: Journal article
Title: Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa
Author: Duncan, L.
Yilmaz, Z.
Gaspar, H.
Walters, R.
Goldstein, J.
Anttila, V.
Bulik-Sullivan, B.
Ripke, S.
Thornton, L.
Hinney, A.
Daly, M.
Sullivan, P.
Zeggini, E.
Breen, G.
Bulik, C.
Gaspar, H.
Walters, R.
Goldstein, J.
Adan, R.
Alfredsson, L.
et al.
Citation: American Journal of Psychiatry, 2017; 174(9):850-858
Publisher: American Psychiatric Association Publishing
Issue Date: 2017
ISSN: 0002-953X
1535-7228
Statement of
Responsibility: 
Laramie Duncan ... Sarah Cohen-Woods ... et al [Eating Disorders Working Group of the Psychiatric Genomics Consortium]
Abstract: 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 [h2SNP]), 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 h2SNP 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.
Keywords: Eating disorders; genetics; anorexia nervosa; metabolism; GWAS; diabetes
Rights: Copyright Status Unknown
RMID: 0030118558
DOI: 10.1176/appi.ajp.2017.16121402
Grant ID: http://purl.org/au-research/grants/nhmrc/324715
http://purl.org/au-research/grants/nhmrc/480420
http://purl.org/au-research/grants/nhmrc/310667
Appears in Collections:Medicine publications

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