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Application of Laser Microdissection to Uncover Regional Transcriptomics in Human Kidney Tissue
Published on: June 9, 2020
A Cross-Tissue Transcriptome-Wide Association Study Identifies Novel Susceptibility Genes for Glomerular Diseases.
Lichao Mao1,2,3,4, Linhong Xu1,2,3,4, Tong Zhu1,2,3,4
1Renal Division, Peking University Institute of Nephrology, Peking University First Hospital, Beijing 100034, China.
Biomedicines
|May 27, 2026
Summary
This study identifies novel genes contributing to glomerular diseases (GD) using a cross-tissue transcriptome-wide association study (TWAS) and Mendelian randomization (MR). It highlights potential new therapeutic targets for GD, advancing precision nephrology.
Area of Science:
- Genetics
- Nephrology
- Genomics
Background:
- Glomerular diseases (GD) have complex genetic origins, with many causal genes remaining unknown.
- Genome-wide association studies (GWAS) often identify variants in non-coding regions, limiting direct gene identification.
- Transcriptome-wide association studies (TWAS) offer a powerful approach to link genetic variants to gene expression and disease risk.
Purpose of the Study:
- To systematically identify and validate novel susceptibility genes for glomerular diseases (GD).
- To leverage an integrative cross-tissue TWAS and Mendelian randomization (MR) framework for comprehensive gene discovery.
- To explore potential therapeutic targets for GD based on identified genetic factors.
Main Methods:
- Conducted a systematic cross-tissue TWAS integrating Genotype-Tissue Expression (GTEx) v8 eQTL data across 49 human tissues.
- Employed five complementary frameworks (sCCA, FUSION, FOCUS, SMR, MAGMA) to nominate candidate GD susceptibility genes.
- Refined findings using Mendelian randomization (MR), pathway enrichment, protein interaction networks, and druggability analysis.
Main Results:
- Identified 21 candidate GD susceptibility genes, with 10 strongly supported by MR analysis.
- Discovered five previously unreported GD susceptibility genes: C6orf48, CSNK2B, HSD17B8, LST1, and PRRT1.
- Found prioritized genes involved in immune modulation, inflammation, and steroid metabolism, with five identified as potentially druggable targets.
Conclusions:
- This study presents the first systematic cross-tissue TWAS for GD, prioritizing genetically supported susceptibility genes.
- Uncovered novel genetic drivers and druggable proteins, enhancing the mechanistic understanding of GD.
- Provides a foundation for developing new therapies and advancing precision nephrology for glomerular diseases.
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