Childhood Mental Health and Body Mass Index as Mediators of Genetic Risk for Eating Disorders.

Importance: Eating disorders (EDs) are heritable, yet the developmental pathways through which genetic liability manifests in early life remain unclear. Objective: To investigate the associations between genetic liability for anorexia nervosa (AN) and binge eating (BE) and disordered eating behaviors (DEB) across childhood, and to identify the mediating roles of metabolic and psychosocial traits. Design Setting and Participants: This longitudinal observational study used genomic and behavioral data from the Adolescent Brain Cognitive Development Exposures: Polygenic scores (PGS) for AN and BE were calculated using summary statistics from the most recent genome-wide association studies. Mediators included BMI, ADHD, anxiety/depression, and social problems from the Child Behavioral Checklist assessed at Year 1 follow-up (T1). Main Outcomes and Measures: Parent reported DEB symptoms via the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS). For longitudinal association analyses, DEB were pooled across T0, T1 and T2 to assess the relationship between genetic liability and childhood symptom severity. For mediation analyses, DEB at T2 follow-up were used to ensure a clear temporal sequence between mediators at T1 and the outcomes. Results: Among 5,618 EUR participants (mean [SD] age, 9.91 [0.62] years; 47% female), longitudinal association models revealed that higher AN-PGS was associated with increased AN symptoms, while BE-PGS was associated with increased BE and AN symptoms. These patterns were largely consistent in exploratory cross-ancestry analyses. Mediation analyses showed that BMI mediated genetic risks across sexes, while ADHD and anxiety/depression symptoms emerged as additional mediators in females. Conclusions and Relevance: Genetic liabilities to AN and BE contribute to childhood DEB through sex-dependent pathways, highlighting the developmental continuity of ED risk from childhood. Integrating genetic profiles with behavioral markers may facilitate early identification and support multifaceted interventions.