Genetic Association of CANT1 Gene with Scoliosis: An Integrative Study Involving Methylation, Immune Factors, and Metabolites.

The CANT1 gene, encoding a nucleotidase linked to calcium signaling, is crucial for spinal development, with its deficiency causing skeletal developmental issues. However, the relationship between CANT1 and scoliosis remains unclear. This study aims to explore the role of CANT1 in scoliosis from a genetic perspective and its potential as a therapeutic target. This study employed a multi-method approach, including Mendelian Randomization (MR) analysis, colocalization analysis, mediation analysis, enrichment analysis, PPI network construction, and molecular docking. Using eQTL and pQTL databases, the Inverse Variance Weighted (IVW) method identified key genes associated with scoliosis. Colocalization analysis pinpointed genes with strong causal links to scoliosis. Mediation analysis assessed the impact of CANT1 methylation, immune cells, inflammatory factors, and plasma metabolites on scoliosis. Enrichment analysis identified biological pathways enriched in scoliosis-related genes. The PPI network was constructed using the STRING database, and CANT1 expression in bone marrow and skeletal muscle was analyzed via the Human Protein Atlas. Potential therapeutic compounds were identified through the DSigDB database and validated by molecular docking. We identified 94 key genes associated with scoliosis, primarily involved in purine ribonucleotide metabolism. Colocalization analysis provided strong evidence linking CANT1 to scoliosis. Further analysis revealed that methylation sites, immune cells, inflammatory factors, and plasma metabolites related to CANT1 may play roles in scoliosis pathogenesis. The regulatory expression of CANT1 was examined using the STRING database and the Human Protein Atlas. Six candidate compounds with favorable binding affinity to CANT1 were identified through DSigDB and molecular docking. This study offers new insights into the pathogenesis of scoliosis and highlights CANT1 as a potential therapeutic target. CANT1 may influence scoliosis development through multiple pathways, including methylation, immune cells, inflammatory factors, and plasma metabolites. Further experimental validation is needed to confirm these findings and explore the therapeutic potential of the identified compounds.