ArticleProceedings of the National Academy of Sciences of the United States of America2023
The contributions of rare inherited and polygenic risk to ASD in multiplex families.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 4 of them syntheses that pooled it.
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Who cites it
72 citing papers in PubMed, 4 syntheses or guidelines pooled it, 100 citations in OpenAlex.
- Maternal paracetamol (acetaminophen) use during pregnancy and risk of autism spectrum disorder and attention deficit/hyperactivity disorder in offspring: umbrella review of systematic reviews.BMJ (Clinical research ed.) · 2025Pooled it
- Presymptomatic Biological, Structural, and Functional Diagnostic Biomarkers of Autism Spectrum Disorder.Journal of neurochemistry · 2025Pooled it
- Studies assessing domains pertaining to structural language in autism vary in reporting practices and approaches to assessment: A systematic review.Autism : the international journal of research and practice · 2024Pooled it
- Bridging Genetic Insights with Neuroimaging in Autism Spectrum Disorder-A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Deciphering the genetic basis of developmental language disorder in children without intellectual disability, autism or apraxia of speech.Molecular autism · 2025Trial
- Common genetic variants are associated with increased likelihood of latent co-occurring neurodevelopmental and mental health factors among autistic individuals.Molecular psychiatry · 2026Article
- Elucidating the role of DEAF1 in neurodevelopment and shared molecular pathways in high-risk autism genes using cortical organoids.Science advances · 2026Article
- Systematic CRISPRi perturbation of 1,408 autism risk genes maps multilevel transcriptional convergence in human cortical neurons.bioRxiv : the preprint server for biology · 2026Article
- Article
- Dynamic neuro-immune regulation of psychiatric risk loci in human neurons.Nature communications · 2026Article
- Potential for Genomics to Help Guide Preventive Strategies in Psychiatry.JAMA psychiatry · 2026Article
- Challenging the Developmental Substructure Model for Autism: A Perspective From Causal Statistics.Autism research : official journal of the International Society for Autism Research · 2026Article
- Rationale and Methods for the Prospective Genetic Risk Evaluation and Assessment (PROGRESS) in Autism Center at Columbia University.Pediatric research · 2026Article
- Mapping lncRNAs onto multilevel mRNA co‑expression modules in autism.Translational psychiatry · 2026Article
- The NeuroWES project: lessons learned from comprehensive phenotyping and genetic analysis of neurodevelopmental disorders over a decade.Human genetics · 2026Article
- Review
- Autism-like phenotypes and increased NMDAR2D expression in mice with KDM5B histone lysine demethylase deficiency.Science advances · 2026Article
- Subclinical neuropsychiatric trait variation in parents of children with autism spectrum disorder: a cohort study.Molecular autism · 2026Article
- Illuminating hidden genetic architecture in autism.Cell genomics · 2026Article
- Association between greenspace exposure before, during, and after pregnancy and autism spectrum disorder in offspring.Journal of exposure science & environmental epidemiology · 2026Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Autism spectrum disorder (ASD) has a complex genetic architecture involving contributions from both de novo and inherited variation. Few studies have been designed to address the role of rare inherited variation or its interaction with common polygenic risk in ASD. Here, we performed whole-genome sequencing of the largest cohort of multiplex families to date, consisting of 4,551 individuals in 1,004 families having two or more autistic children. Using this study design, we identify seven previously unrecognized ASD risk genes supported by a majority of rare inherited variants, finding support for a total of 74 genes in our cohort and a total of 152 genes after combined analysis with other studies. Autistic children from multiplex families demonstrate an increased burden of rare inherited protein-truncating variants in known ASD risk genes. We also find that ASD polygenic score (PGS) is overtransmitted from nonautistic parents to autistic children who also harbor rare inherited variants, consistent with combinatorial effects in the offspring, which may explain the reduced penetrance of these rare variants in parents. We also observe that in addition to social dysfunction, language delay is associated with ASD PGS overtransmission. These results are consistent with an additive complex genetic risk architecture of ASD involving rare and common variation and further suggest that language delay is a core biological feature of ASD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.