ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
Regulatory Variant rs2535629 in ITIH3 Intron Confers Schizophrenia Risk By Regulating CTCF Binding and SFMBT1 Expression.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.
- Genome-wide meta-analysis, functional genomics and integrative analyses implicate new risk genes and therapeutic targets for anxiety disorders.Nature human behaviour · 2024Pooled it
- An updated catalog ofFrontiers in molecular neuroscience · 2023Pooled it
- Silencer variants are key drivers of gene up-regulation in Alzheimer's disease.Science advances · 2026Article
- Functional variants at 1p36.23 confer risk of schizophrenia through modulating RERE.Nature communications · 2026Article
- Identifying deleterious noncoding variation through gain and loss of CTCF binding activity.American journal of human genetics · 2025Article
- NEK4 suppresses cell proliferation in BT20 triple-negative breast cancer cells by diminishing expression of cell cycle genes, while its depletion mitigates proliferation in other cell lines.Frontiers in oncology · 2025Article
- Investigating the Shared Genetic Architecture Between Psychiatric Disorders and Executive Function.Biological psychiatry global open science · 2024Article
- Unraveling NEK4 as a Potential Drug Target in Schizophrenia and Bipolar I Disorder: A Proteomic and Genomic Approach.Schizophrenia bulletin · 2024Article
- The contribution of silencer variants to human diseases.Genome biology · 2024Article
- Characteristics of changes in plasma proteome profiling after sleeve gastrectomy.Frontiers in endocrinology · 2024Article
- Shared genetic architecture of psychiatric disorders and hemorrhoidal disease: a large-scale genome-wide cross-trait analysis.Frontiers in psychiatry · 2024Article
- A Functional Schizophrenia-associated genetic variant near thebioRxiv : the preprint server for biology · 2023Article
- 3D genome alterations and editing in pathology.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Regulatory Variant rs2535629 in ITIH3 Intron Confers Schizophrenia Risk By Regulating CTCF Binding and SFMBT1 Expression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Genome-wide association studies have identified 3p21.1 as a robust risk locus for schizophrenia. However, the underlying molecular mechanisms remain elusive. Here a functional regulatory variant (rs2535629) is identified that disrupts CTCF binding at 3p21.1. It is confirmed that rs2535629 is also significantly associated with schizophrenia in Chinese population and the regulatory effect of rs2535629 is validated. Expression quantitative trait loci analysis indicates that rs2535629 is associated with the expression of three distal genes (GLT8D1, SFMBT1, and NEK4) in the human brain, and CRISPR-Cas9-mediated genome editing confirmed the regulatory effect of rs2535629 on GLT8D1, SFMBT1, and NEK4. Interestingly, differential expression analysis of GLT8D1, SFMBT1, and NEK4 suggested that rs2535629 may confer schizophrenia risk by regulating SFMBT1 expression. It is further demonstrated that Sfmbt1 regulates neurodevelopment and dendritic spine density, two key pathological characteristics of schizophrenia. Transcriptome analysis also support the potential role of Sfmbt1 in schizophrenia pathogenesis. The study identifies rs2535629 as a plausibly causal regulatory variant at the 3p21.1 risk locus and demonstrates the regulatory mechanism and biological effect of this functional variant, indicating that this functional variant confers schizophrenia risk by altering CTCF binding and regulating expression of SFMBT1, a distal gene which plays important roles in neurodevelopment and synaptic morphogenesis.
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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 Socratic graph.