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Título:	Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa
Autor/a:	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
Otros autores:	Universitat de Barcelona
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.
Materia(s):	-Anorèxia nerviosa -Genètica -Metabolisme -Anorexia nervosa -Genetics -Metabolism
Derechos:	(c) American Psychiatric Association, 2017
Tipo de documento:	Artículo Artículo - Versión aceptada
Editor:	American Psychiatric Association
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