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|Title:||Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa|
Eating Disorders Working Group of the Psychiatric Genomics Consortium
Thornton, Laura M.
Sullivan, Patrick F.
Bulik, Cynthia M.
Fernández Aranda, Fernando
Rabionet Janssen, Raquel
|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|
|Appears in Collections:||Articles publicats en revistes (Genètica, Microbiologia i Estadística)|
Articles publicats en revistes (Ciències Clíniques)
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