{"doi":"10.1093/jamia/ocab144","title":"Multi-PheWAS intersection approach to identify sex differences across comorbidities in 59 140 pediatric patients with autism spectrum disorder","abstract":"OBJECTIVE: To identify differences related to sex and define autism spectrum disorder (ASD) comorbidities female-enriched through a comprehensive multi-PheWAS intersection approach on big, real-world data. Although sex difference is a consistent and recognized feature of ASD, additional clinical correlates could help to identify potential disease subgroups, based on sex and age. MATERIALS AND METHODS: We performed a systematic comorbidity analysis on 1860 groups of comorbidities exploring all spectrum of known disease, in 59 140 individuals (11 440 females) with ASD from 4 age groups. We explored ASD sex differences in 2 independent real-world datasets, across all potential comorbidities by comparing (1) females with ASD vs males with ASD and (2) females with ASD vs females without ASD. RESULTS: We identified 27 different comorbidities that appeared significantly more frequently in females with ASD. The comorbidities were mostly neurological (eg, epilepsy, odds ratio [OR] > 1.8, 3-18 years of age), congenital (eg, chromosomal anomalies, OR > 2, 3-18 years of age), and mental disorders (eg, intellectual disability, OR > 1.7, 6-18 years of age). Novel comorbidities included endocrine metabolic diseases (eg, failure to thrive, OR = 2.5, ages 0-2), digestive disorders (gastroesophageal reflux disease: OR = 1.7, 6-11 years of age; and constipation: OR > 1.6, 3-11 years of age), and sense organs (strabismus: OR > 1.8, 3-18 years of age). DISCUSSION: A multi-PheWAS intersection approach on real-world data as presented in this study uniquely contributes to the growing body of research regarding sex-based comorbidity analysis in ASD population. CONCLUSIONS: Our findings provide insights into female-enriched ASD comorbidities that are potentially important in diagnosis, as well as the identification of distinct comorbidity patterns influencing anticipatory treatment or referrals. The code is publicly available (https://github.com/hms-dbmi/sexDifferenceInASD).","journal":"Journal of the American Medical Informatics Association","year":2021,"id":203702,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.6715,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":785001,"name":"Carlos Sáez","orcid":"0000-0003-2678-8249","position":1,"is_corresponding":false},{"id":12442,"name":"Carlos De Niz","orcid":null,"position":2,"is_corresponding":false},{"id":785002,"name":"Niloofar Jalali","orcid":"0000-0002-7356-0573","position":3,"is_corresponding":false},{"id":777703,"name":"Thomas DeSain","orcid":null,"position":4,"is_corresponding":false},{"id":489665,"name":"Ranjay Kumar","orcid":null,"position":5,"is_corresponding":false},{"id":785003,"name":"Joany M. Zachariasse","orcid":"0000-0002-4093-8509","position":6,"is_corresponding":false},{"id":252717,"name":"Kathe Fox","orcid":null,"position":7,"is_corresponding":false},{"id":249689,"name":"Nathan Palmer","orcid":"0000-0002-4361-207X","position":8,"is_corresponding":false},{"id":3527,"name":"Isaac S. Kohane","orcid":"0000-0003-2192-5160","position":9,"is_corresponding":false},{"id":74694,"name":"Paul Avillach","orcid":"0000-0002-0235-7543","position":10,"is_corresponding":false},{"id":488860,"name":"Alba Gutiérrez‐Sacristán","orcid":"0000-0002-1245-198X","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T23:51:18.050175Z","pmid":"34405856","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}