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

Abstract

Background Eating disorder treatment is most successful when delivered at first onset, underscoring the importance of early intervention. UK patients transition from child to adult services at age 18, a process often poorly supported. Genetic factors may contribute to earlier onset, but molecular genetic research into symptom onset and severity remains limited. Aims We investigated (1) age at onset of behavioural symptoms and low weight, including sex differences, (2) the SNP based heritability and cross trait polygenic associations of symptoms, onset, and severity. Method Participants (n = 24,973) were from the NIHR BioResource, including the Genetic Links to Anxiety and Depression Study, Eating Disorders Genetics Initiative UK, and COVID19 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 using GCTA GREML. We tested associations with 26 polygenic scores (PGS), which were calculated using SBayesRC. Results Symptom median onset ranged from 16 to 20 years: vomiting (16), fasting and excessive exercise (17), binge eating (18), laxatives (19), diuretics (20), and low weight (20). Males were disproportionately likely to report adult onset. In females, behavioural symptoms and low weight showed substantial heritability (SNP-based h2 = 0.31 to 0.78), but onset and cognitive symptoms appeared to be less heritable. PGS analyses identified distinct pathways: in females, higher childhood obesity PGS was linked to earlier binge eating onset (~7 months), and higher educational attainment PGS to earlier low weight onset (~6 months). Conclusions Eating disorder symptoms begin in adulthood as frequently as adolescence, challenging stereotypes and underscoring investment needed in adult services, particularly for men. While symptoms were strongly heritable, 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.