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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

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.

The nomenclature of personality disorders in the 11th revision of the International Classification of Diseases and Related Health Problems represents the most radical change in the classification history of personality disorders. A dimensional structure now replaces categorical description. It was argued by the Working Group that only a dimensional system was consistent with the empirical evidence and, in the spirit of clinical utility, the new system is based on two steps. The first step is to assign one of five levels of severity, and the second step is to assign up to five prominent domain traits. There was resistance to this structure from those who feel that categorical diagnosis, particularly of borderline personality disorder, should be retained. After lengthy discussion, described in detail here, there is now an option for a borderline pattern descriptor to be selected as a diagnostic option after severity has been determined.

Nineteen years have elapsed since the 10th revision of the International Classification of Diseases (ICD‐10), and many advances have been made in the field of personality disorders since that time. This paper reflects these advances and presents the first proposals of the ICD‐11 working group for the reclassification of personality disorders. The essential changes from ICD‐10 are to make the primary classification of personality disorder one of five levels of severity, including one of personality difficulty below the severity of disorder, to replace the existing categories of personality disorder with five monothetic trait domains of asocial, emotionally unstable, obsessional (anankastic), anxious/dependent and dissocial groups and to provide a simple algorithm for classification that can be used in ordinary psychiatric practice. It is argued that the proposed changes will improve the clinical utility of the diagnosis of personality disorder, reduce its stigma and help in the development and selection of appropriate treatment. Copyright © 2011 John Wiley & Sons, Ltd.