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Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa.

Artikel i vetenskaplig tidskrift
Författare Laramie Duncan
Zeynep Yilmaz
Helena Gaspar
Raymond Walters
Jackie Goldstein
Verneri Anttila
Brendan Bulik-Sullivan
Stephan Ripke
Mikael Landén
Laura Thornton
Anke Hinney
Mark Daly
Patrick F Sullivan
Eleftheria Zeggini
Gerome Breen
Cynthia M Bulik
Publicerad i The American journal of psychiatry
Volym 174
Nummer/häfte 9
Sidor 850-858
ISSN 1535-7228
Publiceringsår 2017
Publicerad vid
Sidor 850-858
Språk en
Länkar dx.doi.org/10.1176/appi.ajp.2017.16...
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämneskategorier Klinisk medicin, Psykiatri

Sammanfattning

The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes.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 [h(2)SNP]), partitioned heritability, and genetic correlations (rg) between anorexia nervosa and 159 other phenotypes.Results were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h(2)SNP 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.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.

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