Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/139926
Title: Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa
Author: Duncan, Laramie
Yilmaz, Zeynep
Gaspar, Helena
Walters, Raymond
Goldstein, Jackie
Anttila, Verneri
Bulik-Sullivan, Brendan
Ripke, Stephan
Eating Disorders Working Group of the Psychiatric Genomics Consortium
Thornton, Laura
Hinney, Anke
Daly, Mark
Sullivan, Patrick F.
Zeggini, Eleftheria
Breen, Gerome
Bulik, Cynthia M.
Fernández Aranda, Fernando
Rabionet Janssen, Raquel
Keywords: Anorèxia nerviosa
Genètica
Metabolisme
Anorexia nervosa
Genetics
Metabolism
Issue Date: 12-May-2017
Publisher: American Psychiatric Association
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.
Note: Versió postprint del document publicat a: https://doi.org/10.1176/appi.ajp.2017.16121402
It is part of: American Journal of Psychiatry, 2017, vol. 174, num. 9, p. 850-858
URI: http://hdl.handle.net/2445/139926
Related resource: https://doi.org/10.1176/appi.ajp.2017.16121402
ISSN: 0002-953X
Appears in Collections:Articles publicats en revistes (Genètica, Microbiologia i Estadística)
Articles publicats en revistes (Ciències Clíniques)

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