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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.

Objective: the aim of this longitudinal study was to evaluate the impact of COVID-19 epidemic on Eating Disorders (EDs) patients, considering the role of pre-existing vulnerabilities. Method: 74 patients with Anorexia Nervosa (AN) or Bulimia Nervosa (BN) and 97 healthy controls (HCs) were evaluated before lockdown (T1) and during lockdown (T2). Patients were also evaluated at the beginning of treatment (T0). Questionnaires were collected to assess psychopathology, childhood trauma, attachment style, and COVID-19-related post-traumatic symptoms. Results: A different trend between patients and HCs was observed only for pathological eating behaviors. Patients experienced increased compensatory exercise during lockdown; BN patients also exacerbated binge eating. Lockdown interfered with treatment outcomes: the descending trend of ED-specific psychopathology was interrupted during the epidemic in BN patients. Previously remitted patients showed re-exacerbation of binge eating after lockdown. Household arguments and fear for the safety of loved ones predicted increased symptoms during the lockdown. BN patients reported more severe COVID-19-related post-traumatic symptomatology than AN and HCs, and these symptoms were predicted by childhood trauma and insecure attachment. Discussion: COVID-19 epidemic significantly impacted on EDs, both in terms of post-traumatic symptomatology and interference with the recovery process. Individuals with early trauma or insecure attachment were particularly vulnerable.

Among EDs, there are different subgroups of patients displaying various courses and outcomes. The diagnostic instability involves the large majority of patients. An integration of categorical and dimensional approaches could improve the psychopathological investigation and the treatment choices.