ArticleGenome medicine2017
Integrated Bayesian analysis of rare exonic variants to identify risk genes for schizophrenia and neurodevelopmental disorders.
Article in Genome medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.
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Who cites it
61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 106 citations in OpenAlex.
- Assessment of the functionality and usability of open-source rare variant analysis pipelines.Briefings in bioinformatics · 2025Pooled it
- Analysing an allelic series of rare missense variants of CACNA1I in a Swedish schizophrenia cohort.Brain : a journal of neurology · 2022Pooled it
- Rationale and Methods for the Prospective Genetic Risk Evaluation and Assessment (PROGRESS) in Autism Center at Columbia University.Pediatric research · 2026Article
- MIRAGE: A Bayesian statistical method for gene-level rare-variant analysis incorporating functional annotations.American journal of human genetics · 2026Article
- Joint analysis ofNAR genomics and bioinformatics · 2025Article
- Analyses of GWAS and Sub-Threshold Loci Lead to the Discovery of Dendrite Development and Morphology Dysfunction Underlying Schizophrenia Genetic Risk.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- NoncodingiScience · 2025Article
- A probabilistic graphical model for estimating selection coefficients of nonsynonymous variants from human population sequence data.Nature communications · 2025Article
- The Role ofmedRxiv : the preprint server for health sciences · 2025Article
- Common variants increase risk for congenital diaphragmatic hernia within the context of de novo variants.American journal of human genetics · 2024Article
- Bayesian Rare Variant Analysis Identifies Novel Schizophrenia Putative Risk Genes.Journal of personalized medicine · 2024Article
- Rare de novo damaging DNA variants are enriched in attention-deficit/hyperactivity disorder and implicate risk genes.Nature communications · 2024Article
- The Importance of Large-Scale Genomic Studies to Unravel Genetic Risk Factors for Autism.International journal of molecular sciences · 2024Review
- Statistical methods for assessing the effects of de novo variants on birth defects.Human genomics · 2024Review
- STIGMA: Single-cell tissue-specific gene prioritization using machine learning.American journal of human genetics · 2024Article
- RNA-binding protein Nocte regulates Drosophila development by promoting translation reinitiation on mRNAs with long upstream open reading frames.Nucleic acids research · 2024Article
- VBASS enables integration of single cell gene expression data in Bayesian association analysis of rare variants.Communications biology · 2023Article
- RGS14 expression in CA2 hippocampus, amygdala, and basal ganglia: Implications for human brain physiology and disease.Hippocampus · 2023Review
- Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations.Nature genetics · 2023Article
- SCGN deficiency is a risk factor for autism spectrum disorder.Signal transduction and targeted therapy · 2023Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 8 institutions in 3 countries.
Funding
Abstract
backgroundIntegrating rare variation from trio family and case-control studies has successfully implicated specific genes contributing to risk of neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASD), intellectual disability (ID), developmental disorders (DDs), and epilepsy (EPI). For schizophrenia (SCZ), however, while sets of genes have been implicated through the study of rare variation, only two risk genes have been identified.
methodsWe used hierarchical Bayesian modeling of rare-variant genetic architecture to estimate mean effect sizes and risk-gene proportions, analyzing the largest available collection of whole exome sequence data for SCZ (1,077 trios, 6,699 cases, and 13,028 controls), and data for four NDDs (ASD, ID, DD, and EPI; total 10,792 trios, and 4,058 cases and controls).
resultsFor SCZ, we estimate there are 1,551 risk genes. There are more risk genes and they have weaker effects than for NDDs. We provide power analyses to predict the number of risk-gene discoveries as more data become available. We confirm and augment prior risk gene and gene set enrichment results for SCZ and NDDs. In particular, we detected 98 new DD risk genes at FDR < 0.05. Correlations of risk-gene posterior probabilities are high across four NDDs (ρ>0.55), but low between SCZ and the NDDs (ρ<0.3). An in-depth analysis of 288 NDD genes shows there is highly significant protein-protein interaction (PPI) network connectivity, and functionally distinct PPI subnetworks based on pathway enrichment, single-cell RNA-seq cell types, and multi-region developmental brain RNA-seq.
conclusionsWe have extended a pipeline used in ASD studies and applied it to infer rare genetic parameters for SCZ and four NDDs ( https://github.com/hoangtn/extTADA ). We find many new DD risk genes, supported by gene set enrichment and PPI network connectivity analyses. We find greater similarity among NDDs than between NDDs and SCZ. NDD gene subnetworks are implicated in postnatally expressed presynaptic and postsynaptic genes, and for transcriptional and post-transcriptional gene regulation in prenatal neural progenitor and stem cells.
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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.