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https://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.F. Zeggini, E. Breen, G. Bulik, C.M. 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 |
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 DGR 3984/08 K01MH093750 K01MH106675 K01MH109782 R01 MH109528 D0886501 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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