Phenotyping of Health Symptoms in over 129,000 Children and Young Adults with ASD

Cluster analysis was used to examine patterns of symptom co-occurrence in individuals with autism spectrum disorder (ASD), aiming to identify symptom-groupings that may reflect distinct phenotypic subtypes. Parent-reported data from 129,228 participants aged 2-30 years were stratified by ASD severity, age, country, participants’ sex, and parent’s education to examine whether symptom co-occurrence patterns were consistent across subpopulations. Across all subpopulations, several symptom clusters consistently emerged: (1) seizures, lethargy, and gastrointestinal symptoms (diarrhea and constipation); (2) bed-wetting, pants-wetting, and pants-soiling; (3) self-injurious behavior, aggression, and destructiveness; (4) repetitive movements and object fixation; (5) atypical food intake (eating too much/too little); and (6) anxiety, sound sensitivity, rigid routines, insistence on sameness, agitation, and shouting. In contrast, sleep problems, hyperactivity, and reduced pain sensitivity did not form stable clusters, suggesting distinct underlying mechanisms. These findings indicate that common underlying mechanisms may drive clusters of symptoms that appear independent on the surface—for example, the co-occurrence of seizures and gastrointestinal disturbances. Systematic phenotyping can help identify such shared mechanisms, clarify biological pathways, and inform interventions capable of simultaneously addressing multiple symptoms. Shifting the focus from isolated symptoms to phenotypes may improve treatment efficiency, reduce polypharmacy, and ultimately enhance clinical outcomes and quality of life.