Abstract
Idiopathic scoliosis (IS) is a complex, multifactorial spinal deformity with a largely elusive etiology. This review synthesizes current research on the genetic and epigenetic factors contributing to IS development and progression. Genome-wide association studies have identified key susceptibility loci—such as LBX1, GPR126, and BNC2—while family and twin studies underscore a significant heritable component. Chromosomal anomalies and polygenic interactions further complicate the genetic landscape. Concurrently, epigenetic mechanisms—including DNA methylation, histone modifications, and non-coding RNAs—have emerged as critical mediators of gene-environment interactions, influenced by factors such as mechanical load, nutrition, and endocrine disruptors. Multi-omic approaches integrating genomics, transcriptomics, and epigenomics offer new insights into pathophysiology and therapeutic targeting. Ethical considerations surrounding genetic testing and the need for population-specific models are also discussed. Ultimately, this review supports a shift toward precision medicine, highlighting the potential of early molecular biomarkers and epigenetic modulation as tools for individualized scoliosis management and intervention.