ArticleScience translational medicine2021
A method to delineate de novo missense variants across pathways prioritizes genes linked to autism.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-evolutionary exome analysis identifies novel type 2 diabetes mellitus genes in the UK Biobank and all of us.PLoS genetics · 2025Pooled it
- PIEZO1-mediated mechanosensation links aging to bladder dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Ultra-rare functional variants reveal early-onset breast cancer risk genes and pathways in the UK Biobank and All of Us Research Program.American journal of human genetics · 2026Article
- Targeted Therapy ofNeurology. Genetics · 2025Article
- Hearing Loss and Audiogenic Seizures Induced by Hypofunctional Prestin Variants.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- mAutism research : official journal of the International Society for Autism Research · 2025Article
- Biallelic loss-of-function variants in GON4L cause microcephaly and brain structure abnormalities.NPJ genomic medicine · 2024Article
- Genome Sequencing Identifies 13 Novel Candidate Risk Genes for Autism Spectrum Disorder in a Qatari Cohort.International journal of molecular sciences · 2024Article
- Functional Studies of Deafness-Associated Pendrin and Prestin Variants.International journal of molecular sciences · 2024Article
- Neurodevelopmental disorders and cancer networks share pathways, but differ in mechanisms, signaling strength, and outcome.NPJ genomic medicine · 2023Article
- Evolutionary Action-Machine Learning Model Identifies Candidate Genes Associated With Early-Onset Coronary Artery Disease.Journal of the American Heart Association · 2023Article
- A cryptic microdeletion del(12)(p11.21p11.23) within an unbalanced translocation t(7;12)(q21.13;q23.1) implicates new candidate loci for intellectual disability and Kallmann syndrome.Scientific reports · 2023Article
- Evolution of cisplatin resistance through coordinated metabolic reprogramming of the cellular reductive state.British journal of cancer · 2023Article
- Functional variants identify sex-specific genes and pathways in Alzheimer's Disease.Nature communications · 2023Article
- Neurodevelopmental disorders and cancer networks share pathways; but differ in mechanisms, signaling strength, and outcome.bioRxiv : the preprint server for biology · 2023Article
- A microdeletion del(12)(p11.21p11.23) with a cryptic unbalanced translocation t(7;12)(q21.13;q23.1) implicates new candidate loci for intellectual disability and Kallmann syndrome.Research square · 2023Article
- Prioritizing de novo autism risk variants with calibrated gene- and variant-scoring models.Human genetics · 2022Article
- Genome interpretation using in silico predictors of variant impact.Human genetics · 2022Review
- Identification of risk genes for Alzheimer's disease by gene embedding.Cell genomics · 2022Article
- EPIMUTESTR: a nearest neighbor machine learning approach to predict cancer driver genes from the evolutionary action of coding variants.Nucleic acids research · 2022Article
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6 authors.
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Abstract
Genotype-phenotype relationships shape health and population fitness but remain difficult to predict and interpret. Here, we apply an evolutionary action method to de novo missense variants in whole-exome sequences of individuals with autism spectrum disorder (ASD) to unravel genes and pathways connected to ASD. Evolutionary action predicts the impact of missense variants on protein function by measuring the fitness effect based on phylogenetic distances and substitution odds in homologous gene sequences. By examining de novo missense variants in 2384 individuals with ASD (probands) compared to matched siblings without ASD, we found missense variants in 398 genes representing 23 pathways that were biased toward higher evolutionary action scores than expected by random chance; these pathways were involved in axonogenesis, synaptic transmission, and neurodevelopment. The predicted fitness impact of de novo and inherited missense variants in candidate genes correlated with the IQ of individuals with ASD, even for new gene candidates. Taking an evolutionary action method, we detected those missense variants most likely to contribute to ASD pathogenesis and elucidated their phenotypic impact. This approach could be applied to integrate missense variants across a patient cohort to identify genes contributing to a shared phenotype in other complex diseases.
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