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
Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
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.
ABSTRACT. Background. Eating disorders in children and adolescents remain a serious cause of morbidity and mortality in children, adolescents, and young adults. The working knowledge of pathophysiology, recognition, and management of eating disorders continues to evolve as research in this field continues.Objectives. This article builds on previous background and position papers outlining issues relevant to the care of the adolescent patient with an eating disorder.Methods. The eating disorder special interest group from the Society for Adolescent Medicine recognized the need to update the state of the art published guidelines for the care of the adolescent patient with an eating disorder. This article was a multidisciplinary, group effort to summarize the current knowledge of best practice in the field.Results. This article summarizes newer findings on pathogenesis and etiology, prevention and screening, risk factors, nutritional issues, care from the primary care clinician's perspective, appropriate use of a multidisciplinary team, and issues of managed care and reimbursement.Conclusions. Primary prevention combined with early recognition and treatment helps decrease morbidity and mortality in adolescents with eating disorders. Pediatrics 2003;111:e98 -e108. URL: http://www. pediatrics.org/cgi/content/full/111/1/e98; adolescent, child, eating disorder, anorexia nervosa, bulimia nervosa.ABBREVIATIONS. AN, anorexia nervosa; BN, bulimia nervosa; ED-NOS, Eating disorder-not otherwise specified; BMI, body mass index. E ating disorders in children and adolescents continue to be a serious problem and may result in premature death or life-long medical and psychosocial morbidity. In 1995, the Journal of Adolescent Health published background and position papers outlining relevant issues in the care of the adolescent with an eating disorder. 1 This article provides an update on the state of the art for the child and adolescent with an eating disorder. Topics covered are pathogenesis and etiology, prevention and screening, risk factors, nutritional issues, aspects of care from a primary care clinician's perspective and goals for a multidisciplinary team, care in the inpatient and outpatient settings, use of clinical pathways, and issues of managed care and proper reimbursement. PATHOGENESIS AND ETIOLOGY OF EATING DISORDERSDespite increasing awareness of the major eating disorders, a specific etiology for the pathogenesis of anorexia nervosa (AN) and bulimia nervosa (BN) remains unclear. Rather than single factor causal theories, eating disorders are now viewed as multifactorial disorders with the symptom pattern representing a final common pathway. 2 Interest has focused variously on the contribution of environmental and social factors, psychological predisposition, and biological vulnerability, with recent familial aggregation studies renewing interest in the contribution of genetic predisposition.Dieting continues to be a common entry point in both syndromes, with the greatest risk being the group of severe dieters. 3 ...
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