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Proteome-wide mendelian randomization identifies therapeutic targets for nephrolithiasis
Li Wang1,2, Kun-Peng Li1,2, Si-Yu Chen1,2
1Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, 730030, People's Republic of China.
Urolithiasis
|September 5, 2024
Summary
This study identified seven plasma proteins causally linked to Kidney Stone Disease (KSD). Findings reveal potential new therapeutic targets for preventing and treating this common disorder.
Area of Science:
- Genetics and Genomics
- Biochemistry
- Pharmacology
Background:
- Kidney Stone Disease (KSD) is a complex condition influenced by genetics and environment, with high recurrence rates.
- Identifying causative factors and therapeutic targets is crucial for managing KSD.
Purpose of the Study:
- To identify plasma proteins causally associated with KSD.
- To explore potential pharmacological targets for KSD treatment.
Main Methods:
- Utilized Mendelian randomization (MR) analysis on UK Biobank and FinnGen R10 data.
- Performed co-localization, enrichment, and phenome-wide association studies (PheWAS).
Main Results:
- Seven plasma proteins (FKBPL, ITIH3, SERPINC1, CACYBP, DAG1, ITIH1, SEMA6C) showed significant causal links to KSD risk.
- Confirmed shared genetic basis and identified key biological pathways involved in KSD.
- Linked these proteins to 356 other diseases via PheWAS, revealing disease interrelations.
Conclusions:
- Established a causal relationship between seven plasma proteins and KSD.
- These proteins represent promising targets for novel KSD therapeutic strategies.
- Highlighted the complex interplay between plasma proteins, KSD, and other diseases.
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