biostudies-literatureTeerikorpi NSontag FoundationSchmidt FuturesNIMH NIH HHSOverlook FoundationUniversity of California, San FranciscoUniversity of CaliforniaNINDS NIH HHSWilliam K. Bowes, Jr. FoundationNational Institutes of HealthNIH HHSEsther A. and Joseph Klingenstein Funddev204295https://www.ebi.ac.uk/biostudies/studies/S-EPMC12273630biostudies-literatureUnknown152(12)Autism spectrum disorder (ASD) and congenital heart disease (CHD) frequently co-occur, yet the underlying molecular mechanisms of this comorbidity remain unknown. Given that children with CHD are identified as newborns, understanding which CHD variants are associated with autism could help select individuals for early intervention. Autism gene perturbations commonly dysregulate neural progenitor cell (NPC) biology, so we hypothesized that CHD genes disrupting neurogenesis are more likely to increase ASD risk. Therefore, we performed an in vitro pooled CRISPR interference screen to identify CHD genes disrupting NPC biology and identified 45 CHD genes. A cluster of ASD and CHD genes are enriched for ciliary biology, and perturbing any one of seven such genes (CEP290, CHD4, KMT2E, NSD1, OFD1,Development (Cambridge, England)Ciliary biology intersects autism and congenital heart disease.PMC12273630R01NS123263R01 NS123263R01MH125516U01MH115747U01 MH11574712189R01 MH125516R01 MH128364R01MH128364Lasser MCNowakowski TJBader EDea JMcCluskey KESun NWang SNguyen CHTeerikorpi NKostyanovskaya ESchmidt JDWillsey AJWillsey HRfalseCiliary biology intersects autism and congenital heart disease.Autism spectrum disorder (ASD) and congenital heart disease (CHD) frequently co-occur, yet the underlying molecular mechanisms of this comorbidity remain unknown. Given that children with CHD are identified as newborns, understanding which CHD variants are associated with autism could help select individuals for early intervention. Autism gene perturbations commonly dysregulate neural progenitor cell (NPC) biology, so we hypothesized that CHD genes disrupting neurogenesis are more likely to increase ASD risk. Therefore, we performed an in vitro pooled CRISPR interference screen to identify CHD genes disrupting NPC biology and identified 45 CHD genes. A cluster of ASD and CHD genes are enriched for ciliary biology, and perturbing any one of seven such genes (CEP290, CHD4, KMT2E, NSD1, OFD1,2025-01-01T00:00:00Z2025 Jun2026-03-18T13:55:56.226Z2025-08-21T09:53:01.557ZS-EPMC122736304055253510.1242/dev.204295