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<p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2026年1月13日

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  • Tiantaixi Tu

摘要

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.