Mapping the genetic landscape of the age at onset and severity of eating disorder symptoms

BACKGROUND: Eating disorder treatment is most successful when delivered at first onset, underscoring the importance of early intervention. Genetic factors may contribute to earlier onset, but molecular genetic research into symptom onset and severity remains limited. AIMS: We investigated: (a) age at onset of behavioural symptoms and low weight, including sex and gender differences; and (b) the single-nucleotide polymorphism (SNP)-based heritability and cross-trait polygenic associations of symptoms, onset, and severity. METHOD: = 24 973) of genetically derived European ancestry were from the National Institute for Health and Care Research BioResource, including the Genetic Links to Anxiety and Depression Study, the Eating Disorders Genetics Initiative UK and the COVID-19 Psychiatry and Neurological Genetics study. Symptoms were assessed with the ED100K questionnaire. We described sex-stratified onset of binge eating, low weight, self-induced vomiting, laxatives, diuretics, excessive exercise, and fasting. SNP-based heritability was estimated with genome-wide complex trait analysis using genomic-relatedness-based restricted maximum-likelihood. We tested associations with 26 polygenic scores (PGS), which were calculated using SBayesRC. RESULTS: = 0.31-0.78), but age at onset and cognitive symptoms were less heritable. PGS analyses identified distinct pathways: in females, higher childhood obesity PGS was linked to earlier binge eating onset (approximately 7 months), and higher educational attainment PGS to earlier low weight onset (approximately 6 months). CONCLUSIONS: Eating disorder symptoms begin in adulthood as frequently as adolescence, challenging stereotypes and underscoring investment needed in adult services, particularly for males. Although behavioural symptoms and low weight were strongly heritable, age at onset and cognitive symptoms showed limited genetic contribution. Symptom-level PGS analyses highlight distinct biological and developmental pathways. Larger sample sizes and more accurate phenotyping are needed.