A multiethnic meta-analysis defined the association of rs12946942 with severe adolescent idiopathic scoliosis

J Hum Genet. 2019 May;64(5):493-498. doi: 10.1038/s10038-019-0575-7. Epub 2019 Feb 21.

Abstract

Adolescent idiopathic scoliosis (AIS) is the most common type of scoliosis. Controlling its curve progression is the most important clinical task. Although recent genome-wide association studies (GWASs) identified several susceptibility loci associated with the development of AIS, the etiology of curve progression has been still unknown. Our previous GWAS has identified that rs12946942 showed significant association with severe AIS. To confirm the association, we conducted an international meta-analysis using four cohorts with different ethnicity. We analyzed 2272 severe AIS cases and 13,859 controls in total, and found the replication of significant association of rs12946942 (combined P = 7.23×10-13; odds ratio = 1.36, 95% confidence interval = 1.25-1.49). In silico analyses suggested that SOX9 is the most likely susceptibility gene for AIS curve progression in the locus.

Publication types

  • Meta-Analysis

MeSH terms

  • Adolescent
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Polymorphism, Genetic*
  • SOX9 Transcription Factor / genetics*
  • Scoliosis / ethnology*
  • Scoliosis / genetics*

Substances

  • SOX9 Transcription Factor
  • SOX9 protein, human