ArticleBrain : a journal of neurology2022
Regulatory variants at 2q33.1 confer schizophrenia risk by modulating distal gene TYW5 expression.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 3 syntheses or guidelines pooled it, 24 citations in OpenAlex.
- Genome-wide association susceptibility loci for cluster headache support a role for inflammation in the pathophysiology.The journal of headache and pain · 2026Pooled it
- The genetic architecture of brainstem structures.Nature communications · 2025Pooled it
- Genome-wide meta-analysis, functional genomics and integrative analyses implicate new risk genes and therapeutic targets for anxiety disorders.Nature human behaviour · 2024Pooled it
- Shared genetic architecture between schizophrenia and gastrointestinal diseases: insights from large-scale genome-wide cross-trait analysis.Annals of general psychiatry · 2026Article
- Functional variants at 1p36.23 confer risk of schizophrenia through modulating RERE.Nature communications · 2026Article
- Schizophrenia-Related Synaptic Dysfunction and Abnormal Sensorimotor Gating in Akap11-Deficient Mice.Schizophrenia bulletin · 2026Article
- Analysis of biased allelic enhancer activity of schizophrenia-linked common variants.Communications biology · 2025Article
- Transcriptional Regulators in the Cerebellum in Chronic Schizophrenia: Novel Possible Targets for Pharmacological Interventions.International journal of molecular sciences · 2025Article
- The Functions and Mechanisms of the Cohesin Complex in Regulating the Fate Determinations of Stem Cells.Research (Washington, D.C.) · 2025Review
- Investigating the Shared Genetic Architecture Between Psychiatric Disorders and Executive Function.Biological psychiatry global open science · 2024Article
- Genetic regulatory and biological implications of the 10q24.32 schizophrenia risk locus.Brain : a journal of neurology · 2023Article
- CRISPR/Cas-Based Approaches to Study Schizophrenia and Other Neurodevelopmental Disorders.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 2 countries.
Funding
Abstract
Genome-wide association studies have shown that genetic variants at 2q33.1 are strongly associated with schizophrenia. However, potential causal variants in this locus and their roles in schizophrenia remain unknown. Here, we identified two functional variants (rs796364 and rs281759) that disrupt CTCF, RAD21 and FOXP2 binding at 2q33.1. We systematically investigated the regulatory mechanisms of these two variants with serial experiments, including reporter gene assays and electrophoretic mobility shift assay. Intriguingly, these two single nucleotide polymorphisms physically interacted with TYW5 and showed the most significant associations with TYW5 expression in human brain. Consistently, CRISPR-Cas9-mediated genome editing confirmed the regulatory effect of the two single nucleotide polymorphisms on TYW5 expression. Additionally, expression analysis indicated that TYW5 was significantly upregulated in brains of schizophrenia cases compared with controls, suggesting that rs796364 and rs281759 might confer schizophrenia risk by modulating TYW5 expression. We over-expressed TYW5 in mouse neural stem cells and rat primary neurons to mimic its upregulation in schizophrenia and found significant alterations in the proliferation and differentiation of neural stem cells, as well as dendritic spine density following TYW5 overexpression, indicating its important roles in neurodevelopment and spine morphogenesis. Furthermore, we independently confirmed the association between rs796364 and schizophrenia in a Chinese cohort of 8202 subjects. Finally, transcriptome analysis revealed that TYW5 affected schizophrenia-associated pathways. These lines of evidence consistently revealed that rs796364 and rs281759 might contribute to schizophrenia risk by regulating the expression of TYW5, a gene whose expression dysregulation affects two important schizophrenia pathophysiological processes (i.e. neurodevelopment and dendritic spine formation).
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.