Eating disorders—including anorexia nervosa (AN), bulimia nervosa and binge-eating disorder—are clinically distinct but exhibit symptom overlap and diagnostic crossover. Genomic analyses have mostly examined AN. Here we conducted a genomic meta-analysis of case–control studies of binge-eating behavior (BE; 39,279 cases, 1,227,436 controls), alongside analyses of AN (24,223 cases, 1,243,971 controls) and its subtypes (all European ancestries). We identified six BE-associated loci, including loci associated with a higher body mass index and impulse-control behaviors. AN genome-wide association studies yielded eight loci, validating six loci. Subsequent polygenic risk score analysis demonstrated an association with AN in two East Asian ancestry studies. BE and AN exhibited similar positive genetic correlations with psychiatric disorders but opposing genetic correlations with anthropometric traits. Most of the genetic signal in BE and AN was not shared with body mass index. We have extended eating disorder genomics beyond AN; future work will incorporate multiple diagnoses and global ancestries.
Jet D Termorshuizen, Helena L Davies, Sang-Hyuck Lee et al.· Nature Mental Health· 0 citations
Copy number variations (CNVs) are a major contributor to the etiology and phenotypic variability in schizophrenia. CNVs are also independently associated with certain neurological, cognitive, and behavioral conditions, yet their role in early neurodevelopment in the context of treatment-resistant schizophrenia remain largely unexplored. This study aimed to investigate the contribution of neurodevelopmental CNVs to early development among individuals with treatment-resistant schizophrenia (TRS). We conducted a structured, systematic, retrospective record review within a case-control analytic framework. Our cases were the group of neurodevelopmental disorder (NDD) CNV carriers (N = 25) identified in the Pennsylvania State Hospital (PASH) cohort of individuals with treatment resistant psychotic symptoms; non-CNV controls were demographically matched individuals with treatment resistant psychotic symptoms (N = 24) from the PASH cohort. We examined the differences in early NDD phenotypes between cases and controls. CNV carriers had a higher total NDD burden score compared to non-CNV controls (z = 2.20, unadjusted p = 0.03, adjusted p = 0.08). Learning disabilities were significantly more prevalent among CNV carriers compared to non-CNV controls (χ2 = 13.437, df = 1, unadjusted p = 0.0002, adjusted p = 0.0015), with 88% of CNV carriers having a history of learning disabilities relative to 38% of non-CNV controls. CNVs carriers with TRS had a higher prevalence of early NDDs compared to non-CNV controls, particularly in learning disabilities. Prospective studies are needed to elucidate the mechanisms linking CNVs, neurodevelopmental phenotypes, and disease progression in treatment resistant schizophrenia.
Wenxin Bian, R. M. Xavier, T. Dietterich et al.· Biological Research for Nurs...· 0 citations
