The genetic architecture of idiopathic scoliosis

Idiopathic scoliosis (IS) is the most common pediatric spinal deformity, affecting 2-3 % of school age children worldwide. This disease is typically classified by age at onset, with the great majority occurring around the time of the adolescent growth spurt, so-called AIS. AIS can progress rapidly, threatening pain, deformity, and pulmonary dysfunction. Heritability of AIS is high, with genetic factors likely explaining over 80 % of disease risk. Population studies have consistently found that AIS is best explained by a polygenic inheritance model, in which many genetic risk factors combine to cause the disease. Population studies have associated AIS with candidate genes, including the LBX1 homeobox transcription factor, and the G protein-coupled receptor GPR126. AIS candidate genes thus far identified function in muscle and nerve specification in early development, suggesting neuromuscular disease origins, but their role in later human development and growth of the axial spine is an unexplored area of developmental biology. Animal models that can address these issues will become a valuable resource for the AIS research community. Likewise continued gene discovery efforts, aided by next-generation genomic platforms, are a priority for the field and will provide the tools for biological investigations of AIS pathogenesis.