J Korean Neurosurg Soc.  2018 Jan;61(1):66-74. 10.3340/jkns.2016.0910.002.

Novel Genetic Variants Associated with Lumbar Spondylosis in Koreans: A Genome-Wide Association Study

• Kim HA
• Heo SG
• Park JW
• Jung YO

• KMID: 2403525
• DOI: http://doi.org/10.3340/jkns.2016.0910.002

Abstract

OBJECTIVE
The aim of this study was to identify the susceptibility genes responsible for lumbar spondylosis (LS) in Korean patients.
METHODS
Data from 1427 subjects were made available for radiographic grading and genome wide association studies (GWAS) analysis. Lateral lumbar spine radiographs were obtained and the various degrees of degenerative change were semi-quantitatively scored. A pilot GWAS was performed using the AffymetrixGenome-Wide Human single-nucleotide polymorphisms (SNPs), 500K array. A total of 352228 SNPs were analyzed and the association between the SNPs and case-control status was analyzed by stepwise logistic regression analyses.
RESULTS
The top 100 SNPs with a cutoff p-value of less than 3.7×10⁻⁴ were selected for joint space narrowing, while a cutoff p-value of 6.0×10⁻⁴ was applied to osteophytes and the Kellgren-Lawrence (K-L) osteoarthritis grade. The SNPs with the strongest effect on disc space narrowing, osteophytes, and K-L grade were serine incorporator 1 (rs155467, odds ratio [OR]=17.58, p=1.6×10⁻⁴), stromal interaction molecule 2 (STIM1, rs210781, OR=5.53, p=5×10⁻⁴), and transient receptor potential cation channel, subfamily C (rs11224760, OR=3.99, p=4.8×10⁻⁴), respectively. Leucine-rich repeat-containing G protein-coupled receptor 4 was significantly associated with both disc space narrowing and osteophytes (rs1979400, OR=2.01, p=1.1×10⁻⁴ for disc space narrowing, OR=1.79, p=3×10⁻⁴ for osteophytes), while zinc finger and BTB domain containing 7C was significantly and negatively associated with both osteophytes and a K-L grade >2 (rs12457004,OR=0.25, p=5.8×10⁻⁴ and OR=0.27, p=5.3×10⁻⁴, respectively).
CONCLUSION
We identified SNPs that potentially contribute to the pathogenesis of LS. This is the first report of a GWAS in an Asian population.

Keyword

Spondylosis; Osteoarthritis; Single nucleotide polymorphism; Genome-wide association study

MeSH Terms

Asian Continental Ancestry Group
Case-Control Studies
Genome-Wide Association Study*
Humans
Joints
Logistic Models
Odds Ratio
Osteoarthritis
Osteophyte
Polymorphism, Single Nucleotide
Serine
Spine
Spondylosis*
Zinc Fingers
Serine

Reference

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