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Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring
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Identification of therapeutic targets for chronic kidney disease through Mendelian randomization analysis of

Run-Sen Liang1, Jin-Qi Su1, Xiang-Qi Wu1

  • 1Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Diseases of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.

Scientific Reports
|March 29, 2025
PubMed

Insights

This study identifies TUBB as a promising drug target for Chronic Kidney Disease (CKD) by analyzing genetic data. Further research into TUBB could lead to new CKD treatments.

Area of Science:

  • Genetics
  • Pharmacology
  • Nephrology

Background:

  • Chronic Kidney Disease (CKD) has limited treatment options due to complex pathogenesis.
  • Novel drug targets are crucial for effective CKD therapy.
  • Genetic studies offer a pathway to identify potential therapeutic targets.

Purpose of the Study:

  • To identify druggable genes associated with Chronic Kidney Disease (CKD) using genetic data.
  • To explore the functional roles of identified genes in CKD pathogenesis.
  • To evaluate TUBB as a potential pharmacological target for CKD treatment.

Main Methods:

  • Utilized cis-expression quantitative trait loci (cis-eQTLs) from eQTLGen as exposure.
  • Employed genome-wide association study (GWAS) data for CKD from FinnGen (11,265 cases, 436,208 controls).
  • Performed Mendelian Randomization (MR), Gene Ontology (GO), KEGG, and colocalization analyses.

Main Results:

  • Identified 12 genes significantly associated with CKD risk (FDR < 0.05).
  • Enrichment analyses revealed involvement in MAP kinase activity, protein kinase activity, Gap junction, Platelet activation, and Oxytocin signaling.
  • Colocalization analysis strongly implicated TUBB gene with CKD (PP.H4 > 80%, TUBB: 97.27%).

Conclusions:

  • TUBB emerges as a highly promising pharmacological target for CKD.
  • This research provides valuable insights for developing novel CKD therapeutics.
  • Genetic association studies are effective in discovering potential drug targets for complex diseases.
Keywords:
Chronic kidney diseaseDruggable genesMendelian randomization analysisTUBB

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