ArticlePLoS genetics2017
Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- Genetic factor analysis for characterizing phenome-wide patterns of genetic pleiotropy.Nature genetics · 2026Article
- Asperger Traits as a Conditionally Adaptive Neurocognitive Phenotype: An Evolutionary Narrative Review.Cureus · 2026Review
- Genomics and multiomics in the age of precision medicine.Pediatric research · 2025Review
- Pan-Cancer Analysis of GPR141: Unveiling its prognostic significance, immune microenvironment interactions, and therapeutic potential.Journal of Cancer · 2025Article
- BridGE: a pathway-based analysis tool for detecting genetic interactions from GWAS.Nature protocols · 2024Review
- Repurposing Niclosamide as a plausible neurotherapeutic in autism spectrum disorders, targeting mitochondrial dysfunction: a strong hypothesis.Metabolic brain disease · 2024Review
- Review
- BiallelicSmall GTPases · 2022Article
- Review
- Genomic selection signatures in autism spectrum disorder identifies cognitive genomic tradeoff and its relevance in paradoxical phenotypes of deficits versus potentialities.Scientific reports · 2021Article
- Alterations in Tau Protein Level and Phosphorylation State in the Brain of the Autistic-Like Rats Induced by Prenatal Exposure to Valproic Acid.International journal of molecular sciences · 2021Article
- Neurofibromatosis Type 1 Implicates Ras Pathways in the Genetic Architecture of Neurodevelopmental Disorders.Behavior genetics · 2020Review
- Genetic Modifiers and Rare Mendelian Disease.Genes · 2020Review
- The Prevalence of Insomnia and the Link between Iron Metabolism Genes Polymorphisms,International journal of environmental research and public health · 2020Article
- Discovering genetic interactions bridging pathways in genome-wide association studies.Nature communications · 2019Article
- Placental DNA methylation levels at CYP2E1 and IRS2 are associated with child outcome in a prospective autism study.Human molecular genetics · 2019Article
- Essential genetic findings in neurodevelopmental disorders.Human genomics · 2019Review
- The Noonan Syndrome-linked Raf1L613V mutation drives increased glial number in the mouse cortex and enhanced learning.PLoS genetics · 2019Article
- Detection of Concordance between Transcriptional Levels of GPCRs and Receptor-Activity-Modifying Proteins.iScience · 2019Article
- Coalitional Game Theory Facilitates Identification of Non-Coding Variants Associated With Autism.Biomedical informatics insights · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Although gene-gene interaction, or epistasis, plays a large role in complex traits in model organisms, genome-wide by genome-wide searches for two-way interaction have limited power in human studies. We thus used knowledge of a biological pathway in order to identify a contribution of epistasis to autism spectrum disorders (ASDs) in humans, a reverse-pathway genetic approach. Based on previous observation of increased ASD symptoms in Mendelian disorders of the Ras/MAPK pathway (RASopathies), we showed that common SNPs in RASopathy genes show enrichment for association signal in GWAS (P = 0.02). We then screened genome-wide for interactors with RASopathy gene SNPs and showed strong enrichment in ASD-affected individuals (P < 2.2 x 10-16), with a number of pairwise interactions meeting genome-wide criteria for significance. Finally, we utilized quantitative measures of ASD symptoms in RASopathy-affected individuals to perform modifier mapping via GWAS. One top region overlapped between these independent approaches, and we showed dysregulation of a gene in this region, GPR141, in a RASopathy neural cell line. We thus used orthogonal approaches to provide strong evidence for a contribution of epistasis to ASDs, confirm a role for the Ras/MAPK pathway in idiopathic ASDs, and to identify a convergent candidate gene that may interact with the Ras/MAPK pathway.
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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 Socratic graph.