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.2019-08-122019-08-122017American Journal of Psychiatry, 2017; 174(9):850-8580002-953X1535-7228http://hdl.handle.net/2440/120516Objective: 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.enCopyright Status UnknownEating disorders; genetics; anorexia nervosa; metabolism; GWAS; diabetesJournal article003011855810.1176/appi.ajp.2017.161214020004088920000102-s2.0-85028720725389153Cohen-Woods, S. [0000-0003-2199-6129]