Identification of a susceptibility locus for severe adolescent idiopathic scoliosis on chromosome 17q24.3

PLoS One. 2013 Sep 4;8(9):e72802. doi: 10.1371/journal.pone.0072802. eCollection 2013.

Abstract

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity, affecting around 2% of adolescents worldwide. Genetic factors play an important role in its etiology. Using a genome-wide association study (GWAS), we recently identified novel AIS susceptibility loci on chromosomes 10q24.31 and 6q24.1. To identify more AIS susceptibility loci relating to its severity and progression, we performed GWAS by limiting the case subjects to those with severe AIS. Through a two-stage association study using a total of ∼12,000 Japanese subjects, we identified a common variant, rs12946942 that showed a significant association with severe AIS in the recessive model (P=4.00 × 10(-8), odds ratio [OR]=2.05). Its association was replicated in a Chinese population (combined P=6.43 × 10(-12), OR = 2.21). rs12946942 is on chromosome 17q24.3 near the genes SOX9 and KCNJ2, which when mutated cause scoliosis phenotypes. Our findings will offer new insight into the etiology and progression of AIS.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Chromosomes, Human, Pair 17 / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study / methods*
  • Genotype
  • Humans
  • Linkage Disequilibrium / genetics
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Scoliosis / etiology
  • Scoliosis / genetics*
  • Young Adult

Grants and funding

The authors have no support or funding to report.