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Comprehensive and integrative analyses identify TYW5 as a schizophrenia risk gene
Chengcheng Zhang1, Xiaojing Li1, Liansheng Zhao1
1Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
BMC Medicine
|May 8, 2022
Summary
TYW5 is a risk gene for schizophrenia (SCZ). This study linked TYW5 gene expression to SCZ risk and brain structure changes, enhancing understanding of SCZ pathogenesis.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Schizophrenia (SCZ) pathogenesis involves complex genetic factors.
- Identifying causal genes at SCZ risk loci is a significant challenge.
- Understanding gene expression's role in SCZ susceptibility is crucial.
Purpose of the Study:
- To explore SCZ risk variants associated with gene expression in the human brain.
- To identify genes contributing to SCZ susceptibility.
- To integrate genetic, gene expression, and brain imaging data for SCZ.
Main Methods:
- Systematic integration of SCZ genome-wide association study (GWAS) data with brain expression quantitative trait loci (eQTL) data.
- Application of Bayesian statistical framework (Sherlock) and Summary data-based Mendelian Randomization (SMR).
- Structural MRI analysis of brain structure in SCZ patients and healthy controls.
Main Results:
- TYW5 mRNA expression significantly associated with SCZ risk via Sherlock and SMR analyses.
- TYW5 protein abundance and expression were significantly higher in SCZ cases.
- The SNP rs203772 linked to SCZ risk and altered TYW5 expression and brain structure.
Conclusions:
- TYW5 is confirmed as a risk gene for schizophrenia.
- Results offer insights into the genetic mechanisms of TYW5 in SCZ.
- This study advances the understanding of SCZ genetic underpinnings.
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