A Replication Study for Association of 53 Single Nucleotide Polymorphisms in ScoliScore Test With Adolescent Idiopathic Scoliosis in French-Canadian Population

Abstract

In Brief Study Design. A replication association study that used genomic data generated from French-Canadian case and control cohorts. Objectives. To determine whether the 53 single nucleotide polymorphisms (SNPs) that were previously associated with spinal deformity progression in an American Caucasian cohort are similarly associated in French-Canadian population. Summary of Background Data. It is widely accepted that genetic factors contribute to adolescent idiopathic scoliosis. The identification of genetic variants associated with the predisposition or progression of curvature could facilitate diagnostic/prognostic tool development. Although 53 SNPs have been associated with spinal curve progression in Caucasian cohorts in the United States, these associations were not replicated in a large Japanese population study, arguing that such a discrepancy could be explained by ethnicity, thus raising the importance of a replication study in an independent Caucasian population of European descent. Methods. Genomic data were collected from the French-Canadian population, using the Illumina HumanOmni 2.5M BeadChip. Fifty-two SNPs, tested in ScoliScore or in high linkage disequilibrium with SNPs in the test, were selected to assess their association with scoliosis generally, and with spinal curve progression. One SNP in ScoliScore, rs16909285, could not be evaluated in our Genome-Wide association study. Results. None of the SNPs used in ScoliScore were associated with adolescent idiopathic scoliosis curve progression or curve occurrence in French-Canadian population. We evaluated 52 SNPs in severe patients by comparing risk allele frequencies with those in nonsevere patients and with those in control individuals. There was no significant difference between the severe group and the nonsevere group or between the severe group and the control group. Conclusion. Although the 52 SNPs studied here were previously associated with curve progression in an American population of European descent, we found no association in French-Canadian patients with adolescent idiopathic scoliosis. This second replication cohort suggests that the lack of association of these SNPs in a Japanese cohort is not due to ethnicity. Level of Evidence: 4 The association of 53 single nucleotide polymorphisms to scoliosis progression has been reported in a Caucasian population, generating a commercial product (ScoliScore) that evaluates risk of curve progression. A previous study using a Japanese population failed to replicate the association. Our study indicates no genetic association between these single nucleotide polymorphisms and adolescent idiopathic scoliosis among French-Canadian population.