Anorexia nervosa polygenic risk, beyond diagnoses: relationship with adolescent disordered eating and behaviours in an Australian female twin population

Background: It is well established that there is a substantial genetic component to eating disorders. Polygenic risk scores (PRS) can be used to quantify cumulative genetic risk for a trait at an individual level. Recent studies suggest PRS for Anorexia Nervosa (AN) may also predict risk for other disordered eating behaviours, but no study has examined if PRS for AN can predict disordered eating as a global continuous measure. This study aimed to investigate whether PRS for AN predicted overall levels of disordered eating, or specific lifetime disordered eating behaviours, in an Australian adolescent female population. Methods: PRS were calculated based on summary statistics from the largest Psychiatric Genomics Consortium AN genome-wide association study to date. Analyses were performed using GCTA to test the associations between AN PRS and disordered eating global scores, avoidance of eating, objective bulimic episodes, self-induced vomiting, and driven exercise in a sample of Australian adolescent female twins recruited from the Australian Twin Registry (N = 383). Results: After applying the false discovery rate correction, the AN PRS was significantly associated with all disordered eating outcomes. Conclusions: Findings suggest shared genetic aetiology across disordered eating presentations and provide insight into the utility of AN PRS for predicting disordered eating behaviours, and individuals at risk, in the general population. In the future, PRSs for eating disorders may have clinical utility in early disordered eating risk identification, prevention, and intervention. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by Grants 324715 and 480420 from the National Health and Medical Research Council (NHMRC) to TDW supported this work. Administrative support for data collection was received from the Australian Twin Registry, which is supported by an Enabling Grant (ID 310667) from the NHMRC administered by the University of Melbourne. The Breakthrough Mental Health Foundation supported the genotyping at Erasmus Medical Centre. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Flinders University Clinical Research Ethics Committee of Flinders University gave ethical approval for this work (no. 115/07) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available from the corresponding author upon reasonable request.