Highlights d Three groups of highly genetically-related disorders among 8 psychiatric disorders d Identified 109 pleiotropic loci affecting more than one disorder d Pleiotropic genes show heightened expression beginning in 2 nd prenatal trimester d Pleiotropic genes play prominent roles in neurodevelopmental processes Authors Cross-Disorder Group of the Psychiatric Genomics Consortium

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Objective To conduct a genome-wide association study (GWAS) of anorexia nervosa and to calculate genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. Method Following uniform quality control and imputation using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, we performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression (LDSC) was used to calculate genome-wide common variant heritability [ hSNP2, partitioned heritability, and genetic correlations (rg)] between anorexia nervosa and other phenotypes. Results Results were obtained for 10,641,224 single nucleotide polymorphisms (SNPs) and insertion-deletion variants with minor allele frequency > 1% and imputation quality scores > 0.6. The hSNP2 of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. We identified one genome-wide significant locus on chromosome 12 (rs4622308, p=4.3×10−9) 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 (HDL) cholesterol, and significant negative genetic correlations between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. Conclusions Anorexia nervosa is a complex heritable phenotype for which we have found the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. Our results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

Objective The aim of this study was to examine anorexics' attitudes towards anorexia nervosa. Method Anorexic patients were asked to write two letters to their anorexia nervosa, one addressing it as a friend and the other addressing it as an enemy. A coding scheme was developed using a “Grounded Theory” methodology to group recurrent themes. The scheme was used independently by three raters: the first author, a rater with extensive experience in eating disorders, and a novice in the field. Use of the coding scheme showed high interrater reliability and comprehensiveness. Results Commonly expressed benefits of anorexia nervosa included feeling looked after or protected, gaining a sense of control, and feeling special. Perceived costs of the disorder included constant thoughts about food, feeling taken over, and the damage done to personal relationships. Discussion The positive themes found in the letters are important indicators of factors which may maintain anorexia nervosa. The use of the letters to examine these factors has important clinical implications which are outlined. © 1999 by John Wiley & Sons, Inc. Int J Eat Disord 25: 177–186, 1999.