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Updated: May 26, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Potential circadian rhythm-related pathogenic genes in diabetic nephropathy: a multi-omics Mendelian randomization
Yanwen Mao1, Minghao Zhang1, Xiaojuan Li1
1Academy of Medical, Henan University of Chinese Medicine, Zhengzhou, Henan, China.
None:
This study aims to identify pathogenic genes involved in diabetic nephropathy (DN) through multi-omics analysis of circadian rhythm disruptions to uncover targets for precision medicine. We conducted summary-data-based Mendelian Randomization (SMR) and colocalization analyses using multi-omics quantitative trait loci (QTL) data (methylation quantitative trait loci [mQTL] , expression quantitative trait loci [eQTL], protein quantitative trait loci [pQTL]) to explore genetic associations between circadian rhythm-related genes and DN. Genome-wide association study (GWAS) summary statistics were sourced from major consortia (discovery) and FinnGen (replication). Key gene expressions were validated in GEO (GSE96804). Transcription factors were predicted, and potential drugs (via Enrichr) were assessed through molecular docking. This study identified 395 methylation loci, 29 genes, and 5 proteins linked to disease using blood-derived QTL data. Replication confirmed 62 methylation loci, 5 genes, and 1 protein were associated with DN. Seven methylation loci influenced four DN-related genes (BICC1, ANKIB1, KIF11, GNAI2). Kidney tissues from DN patients showed elevated GNAI2 and KIF11 but reduced PEBP1. IRF2 was identified as a potential key transcription regulator. Drug predictions suggested calycosin, nitrofural, and nobiletin could target PEBP1, GNAI2, and KIF11, respectively. This SMR study suggested the causal role of circadian rhythm dysfunction in DN. Future research should focus on identifying specific genetic drivers, and exploring therapeutic strategies targeting circadian pathways to mitigate DN progression.
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