Genome-wide association study identifies novel susceptible loci and highlights Wnt/beta-catenin pathway in the development of adolescent idiopathic scoliosis

Hum Mol Genet. 2017 Apr 15;26(8):1577-1583. doi: 10.1093/hmg/ddx045.

Abstract

The genetic architecture of adolescent idiopathic scoliosis (AIS) remains poorly understood. Here we present the result of a 4-stage genome-wide association study composed of 5,953 AIS patients and 8,137 controls. Overall, we identified three novel susceptible loci including rs7593846 at 2p14 near MEIS1 (Pcombined = 1.19 × 10-13, OR = 1.21, 95% CI = 1.10-1.32), rs7633294 at 3p14.1 near MAGI1 (Pcombined = 1.85 × 10-12, OR = 1.20, 95% CI = 1.09-1.32), and rs9810566 at 3q26.2 near TNIK (Pcombined = 1.14 × 10-11, OR = 1.19, 95% CI = 1.08-1.32). We also confirmed a recently reported region associated with AIS at 20p11.22 (Pcombined = 1.61 × 10-15, OR = 1.22, 95% CI = 1.12-1.34). Furthermore, we observed significantly asymmetric expression of Wnt/beta-catenin pathway in the bilateral paraspinal muscle of AIS patients, including beta-catenin, TNIK, and LBX1. This is the first study that unveils the potential role of Wnt/beta-catenin pathway in the development of AIS, and our findings may shed new light on the etiopathogenesis of AIS.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adolescent
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Female
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Germinal Center Kinases
  • Guanylate Kinases
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Protein-Serine-Threonine Kinases / genetics*
  • Scoliosis / genetics*
  • Scoliosis / pathology
  • Transcription Factors / biosynthesis
  • Wnt Signaling Pathway
  • beta Catenin / biosynthesis
  • beta Catenin / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal
  • Germinal Center Kinases
  • Homeodomain Proteins
  • LBX1 protein, human
  • MEIS1 protein, human
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins
  • Transcription Factors
  • beta Catenin
  • Protein-Serine-Threonine Kinases
  • TNIK protein, human
  • Guanylate Kinases
  • MAGI1 protein, human