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 most threatening public health challenges today are chronic and complex and require joint effort from academic researchers in partnership with clinical and public health practitioners to identify and implement sustainable solutions that work in the real world. Practice-based research offers researchers and practitioners an underutilized way forward, an opportunity to work together to design and test feasible, evidence-based programs to address our greatest challenges. In this article, we outline the need for practice-based evidence, tools, and strategies that investigators can use to generate practicebased evidence, describe approaches to translating practice-based evidence into practice, and offer recommendations for making practice-based research the norm in public health.
Individuals with BED had substantially higher healthcare utilization and costs in the years prior to and after diagnosis of BED. Since previous research shows a delay in diagnosis, findings indicate clear opportunities for earlier detection and clinical management. Training of providers in detection, diagnosis, and management may help curtail morbidity. A reduction in healthcare utilization was observed after BED diagnosis. This suggests that earlier diagnosis and treatment could improve long-term health outcomes and reduce the economic burden associated with BED.
Background: The Binge Eating Genetics Initiative (BEGIN) is a multipronged investigation examining the interplay of genomic, gut microbiota, and behavioral factors in bulimia nervosa and binge-eating disorder. Methods: 1000 individuals who meet current diagnostic criteria for bulimia nervosa or binge-eating disorder are being recruited to collect saliva samples for genotyping, fecal sampling for microbiota characterization, and recording of 30 days of passive data and behavioral phenotyping related to eating disorders using the app Recovery Record adapted for the Apple Watch. Discussion: BEGIN examines the interplay of genomic, gut microbiota, and behavioral factors to explore etiology and develop predictors of risk, course of illness, and response to treatment in bulimia nervosa and binge-eating disorder. We will optimize the richness and longitudinal structure of deep passive and active phenotypic data to lay the foundation for a personalized precision medicine approach enabling just-in-time interventions that will allow individuals to disrupt eating disorder behaviors in real time before they occur.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.