A multi-ethnic meta-analysis confirms the association of rs6570507 with adolescent idiopathic scoliosis

Abstract

Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity and has a significant genetic background. Genome-wide association studies (GWASs) identified several susceptibility loci associated with AIS. Among them is a locus on chromosome 6q24.1 that we identified by a GWAS in a Japanese cohort. The locus is represented by rs6570507 located within GPR126. To ensure the association of rs6570507 with AIS, we conducted a meta-analysis using eight cohorts from East Asia, Northern Europe and USA. The analysis included a total of 6,873 cases and 38,916 controls and yielded significant association (combined P = 2.95 × 10^-20; odds ratio = 1.22), providing convincing evidence of the worldwide association between rs6570507 and AIS susceptibility. In silico analyses strongly suggested that GPR126 is a susceptibility gene at this locus.

Figure 1

The flow diagram of the meta-analysis using eight cohorts. Three cohorts (Japanese GWAS, replication study and Nanjing study) were previously reported, and the other five were recruited for this analysis.

Figure 2

The Hi-C interaction surrounding the AIS associated region on chromosome 6q24.1. Hi-C interaction in H1-mesenchymal stem cell was generated by using the Interactive Hi-C Data Browser. GPR126 and VTA1 lie within the topologically associated domain (black triangle) that contains the linkage disequilibrium (LD) block (bold line) of AIS associated SNPs. An arrow indicates the location of rs6570507.