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GWAS identifies 12 new potential susceptibility genes for OPLL
DOI:10.1038/bonekey.2014.112
The authors performed a genome-wide association study (GWAS) to uncover genetics factors relevant in ossification of the posterior longitudinal ligament of the spine (OPLL), a common spinal disorder in the elderly population causing significant morbidity.
Data from 1112 Japanese patients with OPLL and 6810 controls identified 26 single nucleotide polymorphisms (SNPs) within 6 regions on chromosomes 8, 12 and 20 that had an association with OPLL that reached genome-wide significance. These associations were confirmed after genotyping an additional set of 548 Japanese OPLL patients.
The top 6 susceptibility loci were found to contain 12 unique genes. None of these were the same as the 15 gene loci previously reported as being associated with this disease but one was located within the same linkage region as one of the genes identified here.
Of the novel susceptibility genes, RSPH9 and STK38L are involved in the membranous ossification process, and HAO1, RSPO2 and CCDC91 in the endochondral ossification process. RSP02, for example, codes for a secreted protein that is part of the R-spondin family. These proteins are known to be essential for osteoblastogenesis and act through canonical Wnt-signalling to activate β–catenin.
Editor’s comment: Further clarification of genetic association of these genes with OPLL as well as their functional role in the pathogenesis of OPLL should help elucidating the etiology of this disease.
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