Scoliosis Research Society
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Annual Meeting 2019 Hibbs Award Paper Summary

A Multi-ethnic Meta-analysis Defined the Association of rs12946942 with Progression of Adolescent Idiopathic Scoliosis

The authors have identified a new gene SOX9, associated with the progression of Adolescent Idiopathic Scoliosis (AIS).

Scoliosis, an abnormal, lateral curvature of the spine, caused by neurological or muscular diseases, spinal malformations, etc.; however, most of them are idiopathic scoliosis, i.e., those with an unknown cause. The most common occurrence of idiopathic scoliosis is AIS that occurs during puberty. Genetic factors are thought to be involved in the development of AIS, and the susceptibility genes are still being explored worldwide. The authors’ team conducted a genome-wide association studies (GWASs) and found genes LBX1, GPR126, and BNC2, involved in determining the susceptibility to AIS. However, the genetic factors involved in the progression of AIS have not been elucidated yet. Recently, the authors’ team found a susceptibility locus for severe AIS, rs12946942. This time, the authors conducted an international meta-analysis for severe AIS using the genotype datasets in four cohorts belonging to different ethnicities.

The authors investigated 2,272 cases of severe AIS with scoliosis of more than 40° and 13,859 controls from Japan, Nanjing, Hong Kong, and Scandinavia in the current study. They examined approximately 4 million single nucleotide polymorphisms (SNP) covering the entire human genome, and found rs12946942 to have a very strong correlation with severe AIS. This SNP was present in the vicinity of the gene SOX9. Furthermore, using a database, they found that this SNP regulates SOX9 expression in various tissues. SOX9 is one of the most important genes that controls cartilage differentiation, and mutation in it is known to cause campomelic dysplasia, which is characterized by severe scoliosis, more than that due to AIS. The present study revealed that this SNP may affect the expression of SOX9, thereby increasing the severity of AIS. By integrating the world's largest GWAS in scoliosis among multiple races, this study discovered involvement of SOX9 in the progression of AIS, and studied its function at the molecular level. Through understanding the functions of SOX9 in greater detail, new treatment strategies for AIS may be developed in the future.


Summary provided by: SRS Patient Education Committee