ArticleFrontiers in psychiatry2020
Analysis of GWAS-Derived Schizophrenia Genes for Links to Ischemia-Hypoxia Response of the Brain.
Article in Frontiers in psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Interaction between the brain and multiple organ systems in schizophrenia.World journal of psychiatry · 2025Review
- Perinatal Hypoxia and Immune System Activation in Schizophrenia Pathogenesis: Critical Considerations During COVID-19 Pandemic.Physiological research · 2024Review
- Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission.Molecular psychiatry · 2024Article
- Whole-exome sequencing of individuals from an isolated population under extreme conditions implicates rare risk variants of schizophrenia.Translational psychiatry · 2024Article
- Divergent epigenetic responses to perinatal asphyxia in severe mental disorders.Translational psychiatry · 2024Article
- Altered Sphingolipid Hydrolase Activities and Alpha-Synuclein Level in Late-Onset Schizophrenia.Metabolites · 2023Article
- Isoform-level transcriptome-wide association uncovers genetic risk mechanisms for neuropsychiatric disorders in the human brain.Nature genetics · 2023Article
- Sleep Disorder Kleine-Levin Syndrome (KLS) Joins the List of Polygenic Brain Disorders Associated with Obstetric Complications.Cellular and molecular neurobiology · 2023Review
- Mitochondria play an essential role in the trajectory of adolescent neurodevelopment and behavior in adulthood: evidence from a schizophrenia rat model.Molecular psychiatry · 2023Article
- Recent Updates on Corticosteroid-Induced Neuropsychiatric Disorders and Theranostic Advancements through Gene Editing Tools.Diagnostics (Basel, Switzerland) · 2023Review
- Zika virus-induced TNF-α signaling dysregulates expression of neurologic genes associated with psychiatric disorders.Journal of neuroinflammation · 2022Article
- Prediction of Drug Targets for Specific Diseases Leveraging Gene Perturbation Data: A Machine Learning Approach.Pharmaceutics · 2022Article
- CPEB1, a novel risk gene in recent-onset schizophrenia, contributes to mitochondrial complex I defect caused by a defective provirus ERVWE1.World journal of psychiatry · 2021Article
- New and sex-specific migraine susceptibility loci identified from a multiethnic genome-wide meta-analysis.Communications biology · 2021Article
- How do established developmental risk-factors for schizophrenia change the way the brain develops?Translational psychiatry · 2021Review
- Privacy-preserving chi-squared test of independence for small samples.BioData mining · 2021Article
- Fetal Neuroprotective Strategies: Therapeutic Agents and Their Underlying Synaptic Pathways.Frontiers in synaptic neuroscience · 2021Review
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5 authors.
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Abstract
Obstetric complications (OCs) can induce major adverse conditions for early brain development and predispose to mental disorders, including schizophrenia (SCZ). We previously hypothesized that SCZ candidate genes respond to ischemia-hypoxia as part of OCs which impacts neurodevelopment. We here tested for an overlap between SCZ genes from genome-wide association study (GWAS) (n=458 genes from 145 loci of the most recent GWAS dataset in SCZ) and gene sets for ischemia-hypoxia response. Subsets of SCZ genes were related to (a) mutation-intolerant genes (LoF database), (b) role in monogenic disorders of the nervous system (OMIM, manual annotations), and (c) synaptic function (SynGO). Ischemia-hypoxia response genes of the brain (IHR genes, n=1,629), a gene set from RNAseq in focal brain ischemia (BH, n=2,449) and genes from HypoxiaDB (HDB, n=2,289) were overlapped with the subset of SCZ genes and tested for enrichment with Chi-square tests (p < 0.017). The SCZ GWAS dataset was enriched for LoF (n=112; p=0.0001), and the LoF subset was enriched for IHR genes (n=25; p=0.0002), BH genes (n=35; p=0.0001), and HDB genes (n=23; p=0.0005). N=96 genes of the SCZ GWAS dataset (21%) could be linked to a monogenic disorder of the nervous system whereby IHR genes (n=19, p=0.008) and BH genes (n=23; p=0.002) were found enriched. N=46 synaptic genes were found in the SCZ GWAS gene set (p=0.0095) whereby enrichments for IHR genes (n=20; p=0.0001) and BH genes (n=13; p=0.0064) were found. In parallel, detailed annotations of SCZ genes for a role of the hypoxia-inducible factors (HIFs) identified n=33 genes of high interest. Genes from SCZ GWAS were enriched for mutation-intolerant genes which in turn were strongly enriched for three sets of genes for the ischemia-hypoxia response that may be invoked by OCs. A subset of one fifth of SCZ genes has established roles in monogenic disorders of the nervous system which was enriched for two gene sets related to ischemia-hypoxia. SCZ genes related to synaptic functions were also related to ischemia-hypoxia. Variants of SCZ genes interacting with ischemia-hypoxia provide a specific starting point for functional and genomic studies related to OCs.
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