Novel Genetic Variants Associated with Lumbar Spondylosis in Koreans: A Genome-Wide Association Study
10.3340/jkns.2016.0910.002
- Author:
Hyun Ah KIM
1
;
Seong Gu HEO
;
Ji Wan PARK
;
Young Ok JUNG
Author Information
1. Division of Rheumatology, Hallym University Sacred Heart Hospital, Anyang, Korea.
- Publication Type:Original Article
- Keywords:
Spondylosis;
Osteoarthritis;
Single nucleotide polymorphism;
Genome-wide association study
- MeSH:
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
- From:Journal of Korean Neurosurgical Society
2018;61(1):66-74
- CountryRepublic of Korea
- Language:English
-
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.
