Causal relationship between circadian rhythm-related genes expression and spinal disorders: systematic druggable genome-wide Mendelian randomization analysis and virtual screening

📖 Top 30% JournalJan 12, 2026Naunyn-Schmiedeberg's archives of pharmacology

How Daily Rhythm Genes May Influence Spinal Disorders: Genetic Analysis and Drug Screening

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Six spinal disorders are associated with 16 potential circadian genes identified through bioinformatics analysis.

Four genes (KAT5, EZH2, BMP2, EDN1) show moderate to strong evidence of colocalization across multiple spinal disorders.
Pathway analysis indicates involvement of relaxin signaling and longevity regulation in disease mechanisms.
Drug predictions suggest Simvastatin, Niacin, and Acid Red 87 as potential small-molecule therapeutics for further testing.
Causal links between circadian gene dysregulation and spinal diseases were established through integrated data analysis.

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To systematically investigate the causal relationships between circadian rhythm-related genes and the pathogenesis of six spinal disorders (scoliosis, spinal osteochondrosis, instability, stenosis, spondylosis, and spondyloarthritis) using an integrated bioinformatics framework. Mendelian randomization and Bayesian colocalization were applied to cis-eQTL data and GWAS summary statistics. Functional enrichment, protein-protein interaction network analysis, drug prediction, and structure-based virtual screening were subsequently performed. Our research identified 16 potential circadian genes, with four (KAT5, EZH2, BMP2, and EDN1) showing moderate to strong colocalization evidence across multiple disorders. Pathway enrichment highlighted relaxin signaling and longevity regulation. Drug prediction and molecular docking nominated Simvastatin, Niacin, and Acid Red 87 as high affinity candidate compounds. This study establishes causal links between circadian gene dysregulation and spinal diseases, pinpoints key genes and pathways, and proposes potential small-molecule therapeutics for experimental validation.

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