Etiology of developmental spinal stenosis: A genome‐wide association study

Abstract

Our study aimed to identify possible single nucleotide polymorphisms (SNPs) via a genome-wide association study (GWAS) approach and a candidate gene platform that were associated with lumbar developmental spinal stenosis (DSS). Southern Chinese population-based study volunteers were assessed (age range: 18-55 years). DSS was defined as the anteroposterior bony spinal canal diameter on T1-weighted axial MRI of L1 to S1. Genotyping was performed using the Illumina HumanOmniZhongHua-8 BeadChip. Using the canal diameter as the quantitative trait, genomic statistical analyses was performed. A total of 469 subjects were recruited. The mean axial AP measurements noted were: L1: 21.8 mm, L2: 21.9 mm, L3: 22.4 mm, L4: 20.2 mm, L5: 19.6 mm, and S1: 17.3 mm. Q-Q plots of genome-wide associations found significant differences in L4 and L5 measurements. More significant SNPs were found on chromosomes 8, 11, and 18. Low-density lipoprotein receptor-related protein 5 on chromosome 11 was found to be an important functional gene in canal bony development via candidate gene approach. We found two clusters in the findings with one including the upper levels (L1-L4) and the other the lower levels (L5 and S1). This is the first GWAS addressing DSS. The presence of multiple SNPs suggests a multi-factorial origin of DSS. Further analyses noted region-specific genetic predisposition, delineating distinct upper to lower lumbar regions of DSS. With better understanding of the DSS phenotype and genetic markers, the at-risk population can be identified early, preventative measures can be initiated, lifestyle/activity modification can be implemented, and more novel and precision-based therapeutics can be developed. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1262-1268, 2018.

Intelligence-Based Spine Care Model: A New Era of Research and Clinical Decision-Making

“…For the past 20 years, the spine field has seen a surge in studies addressing human genetics and the ability to identify millions of individual single nucleotide polymorphisms in relation to various imaging and/or clinical phenotypes. [36][37][38][39][40][41][42][43][44][45][46][47][48][49] In fact, we have been witnesses to the rise of transcriptomics, proteomics, microbiome, metabolomics and a plethora of other big data "omics" platforms along with their applications toward spine disease. Even the phenotyping of disc cells and other spinal structures, the exponential rise of molecular and biomarker epidemiology, and motion kinematic and analyses further lend to multidimensional big data considerations and integration between different disciplines.…”

The identification of novel gene mutations for degenerative lumbar spinal stenosis using whole-exome sequencing in a Chinese cohort

“…Several studies have identified candidate genes associated with lumbar disc degeneration. Jason et al performed a genome-wide association study and identified multiple SNPs suggesting a multifactorial basis for DLSS [16]. In other work, the HLA-DRB1 genotype increased the risk of developing pain after surgery or lumbar disc herniation [17].…”

Two GWAS-identified variants are associated with lumbar spinal stenosis and Gasdermin-C expression in Chinese population

“…In this study, significant association was only observed in spinal stenosis subgroup, but not in LDH subgroup. This discrepancy could be explained by the fact that LDD has a complex and heterogeneous pathogenesis [29][30][31] . Therefore, from our results, we postulated that these variants may exert more influence in the advanced stages of LDD development in Chinese population.…”