Project Summary
We propose the Eating Disorders Genetics Initiative (EDGI) to rapidly and efficiently advance genomic
discovery across the three major eating disorders (EDs) [AN (anorexia nervosa), BN (bulimia nervosa), and
BED (binge-eating disorder)]. We propose a testable conceptualization of EDs as arising from a shared genetic
vulnerability to a core trait (e.g., dysregulated appetite) that is further differentiated across clinical presentations
of AN, BN, and/or BED by differing genetic predispositions to dimensional ED behaviors (e.g., binge eating,
vomiting, excessive exercise), BMI, personality, comorbid psychopathology, physical activity, and metabolic
traits. We propose that this palette of genetic risk is further influenced by environmental factors that affect
emergence, course, and outcome of the ED. EDGI will empirically test and refine this model. Importantly, we
will ascertain ancestrally diverse cases reflecting known epidemiological distributions of EDs.
Using an efficient online ascertainment approach, EDGI will: (Aim 1) obtain deep phenotyping on course of
illness, comorbid psychiatric conditions, treatment response, healthcare utilization, and quality of life on ~4000
participants in the Anorexia Nervosa Genetics Initiative (ANGI) from the US, Australia (AUS), and New Zealand
(NZ); (Aim 2) ascertain, phenotype, and genotype 4500 new AN cases [(US, AUS, NZ, and Denmark (DK;
identified in national records an genotypes from PKU cards from birth)]; ~5950 BN cases (US, AUS, NZ, DK);
~4050 BED cases (US, AUS, NZ) and 1500 controls; (Aim 3) conduct pre-planned genome-wide association
studies (GWAS) for AN, BN, BED, any ED, and component behaviors, with external replications with Swedish
and Icelandic data, plus a specific set of post-GWAS analyses; (Aim 4) apply advanced analytic strategies to
test and refine our etiological model of EDs to explicate within-ED heterogeneity, explore the genetic relation
between EDs and a broad array of psychiatric, metabolic, anthropometric, physical activity, educational
phenotypes and the forces that shape those relationships, and preliminarily explore polygenic risk (PRS) x
environmental interactions. EDGI represents the next logical step in ED genomics.
Our scientific team recently completed ANGI, yielding compelling genetic findings for AN including the
identification of 8 significant loci and intriguing genetic correlations with both psychiatric and metabolic traits
strongly suggesting that AN is a metabo-psychiatric disorder. EDGI will expand to include BN and BED.
Deliverables include: (a) rich phenotypic and genotypic data on large AN, BN, and BED samples; (b)
clarification of the nature of genetic relationship among EDs and between EDs and other target traits; (c) an
empirical model of ED risk and differentiation; (d) preliminary insight into how genes and environment interact
in EDs; (e) sample and data deposit per current legal and regulatory standards and publicly available summary
statistics. Our ultimate goal aligns with the Psychiatric Genomics Consortium (PGC) by delivering “actionable”
findings that will be transformable into biologically, clinically, and therapeutically meaningful insights on EDs.