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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

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 investigate which sociodemographic factors and behaviors are associated with breakfast skipping in adolescents and adults. Design: Five birth cohorts of adolescent twins and their parents received an extensive behavioral and medical self-report questionnaire that also assessed breakfast-eating frequency. Setting : Finland, 1991: Finland, -1995 Subjects: A population sample of 16-y-old girls and boys (n ¼ 5448) and their parents (n ¼ 4660). Results: Parental breakfast eating was the statistically most significant factor associated with adolescent breakfast eating. Smoking, infrequent exercise, a low education level at 16, female sex, frequent alcohol use, behavioral disinhibition, and high body mass index (BMI) were significantly associated with adolescent breakfast skipping. In adults, smoking, infrequent exercise, low education level, male sex, higher BMI, and more frequent alcohol use were associated with breakfast skipping. In the adult sample, older individuals had breakfast more often than younger ones. Both adults and adolescents who frequently skipped breakfast were much more likely to exercise very little compared to those who skipped breakfast infrequently. Breakfast skipping was associated with low family socioeconomic status in adults and adolescent boys, but not in girls. Breakfast skipping clustered moderately with smoking, alcohol use, and sedentary lifestyle in both adults and adolescents. Conclusions: Breakfast skipping is associated with health-compromising behaviors in adults and adolescents. Individuals and families who skip breakfast may benefit from preventive efforts that also address risk behaviors other than eating patterns.

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 authors found a substantially higher lifetime prevalence and incidence of anorexia nervosa than reported in previous studies, most of which were based on treated cases. Most women recovered clinically within 5 years, and thereafter usually progressed toward full recovery.

Purpose of review: Binge eating disorder (BED) is a new This narrative review provides an overview of the epidemiology of BED, emphasizing studies published in 2018-21.Recent findings: DSM-5 BED is currently estimated to affect 1.5% of women and 0.3% of men worldwide; a lifetime diagnosis of DSM-5 BED is reported by 0.6%-1.8% of women and 0.3%-0.7% of men. In adolescence, BED is even more prevalent but often transient.Many adults with BED report longstanding symptoms; less than half are recognized in healthcare. Commonly co-occuring conditions include obesity, type 2 diabetes, and hypertension. In a nationally representative US-based study, up to 23% of individuals with BED had attempted suicide, and virtually all (94%) reported lifetime mental health symptoms: 70% mood disorders, 68% substance use disorders, 59% anxiety disorders, 49% borderline personality disorder, and 32% posttraumatic stress disorder. Data on mortality are scarce, but the standardized mortality ratio of BED is estimated to be 1.5-1.8. Various minority statuses, deprivation, violence, trauma, and major mental illness may increase the risk of BED. Summary: BED is often invisible and overlooked, perhaps due to societal biases. For this reason, prevention, detection, and management of BED is closely linked with social justice and equity.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10-7) in SOX2OT and rs17030795 (P=5.84×10-6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10-6) between CUL3 and FAM124B and rs1886797 (P=8.05×10-6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4×10-6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.