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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.

Purpose This study examined associations of gender identity and sexual orientation with self-reported eating disorder (SR-ED) diagnosis and compensatory behaviors (CB) in trans- and cis-gender college students. Methods Data came from 289,024 students from 223 U.S. universities participating in The American College Health Association – National College Health Assessment II (median age 20 years). Rates of self-reported past year SR-ED diagnosis and past month use of diet pills and vomiting or laxatives were compared among transgender students (n=479) and cisgender sexual minority male (n=5,977) and female (n=9,445), unsure male (n=1,662) and female (n=3,395), and heterosexual male (n=91,599) and female (n=176,467) students using chi-squared tests. Logistic regression models were used to estimate the odds of eating-related pathology outcomes after adjusting for covariates. Results Rates of past year SR-ED diagnosis and past month use of diet pills and vomiting or laxatives were highest among transgender students and lowest cisgender heterosexual men. Compared to cisgender heterosexual women, transgender students had greater odds of past year SR-ED diagnosis (OR: 4.62, 95% CI: 3.41-6.26) and past month use of diet pills (OR: 2.05, 95% CI: 1.48-2.83) and vomiting or laxatives (OR: 2.46, 95% CI: 1.83-3.30). Although cisgender sexual minority men and unsure men and women also had elevated rates of SR-ED diagnosis than heterosexual women, the magnitudes of these associations were lower than for transgender individuals (ORs: 1.40-1.54). Conclusions Transgender and cisgender sexual minority young adults have elevated rates of CB and SR-ED diagnosis. Appropriate interventions for these populations are urgently needed.

Objective In 2015, the Academy for Eating Disorders (AED) collaborated with international patient, advocacy, and parent organizations to craft the “Nine Truths About Eating Disorders.” This document has been translated into over 30 languages and has been distributed globally to replace outdated and erroneous stereotypes about eating disorders with factual information. In this paper, we review the state of the science supporting the Nine Truths. Methods The literature supporting each of the Nine Truths was reviewed, summarized, and richly annotated. Results Most of the Nine Truths arise from well-established foundations in the scientific literature. Additional evidence is required to further substantiate some of the assertions in the document. Future investigations are needed in all areas to deepen our understanding of eating disorders, their causes, and their treatments. Conclusions The “Nine Truths About Eating Disorders” is a guiding document to accelerate global dissemination of accurate and evidence-informed information about eating disorders.