Attempt to replicate the published osteoarthritis associated genetic variants in the Newfoundland & Labrador Population
Journal Title: Journal of Orthopedics & Rheumatology - Year 2014, Vol 1, Issue 3
Abstract
Objective: Over 200 genes have been reported to be associated with osteoarthritis (OA), but most of them have not been replicated in an independent sample. Using the newly collected cohort from a genetically isolated population - the Newfoundland and Labrador population, we attempted to replicate 105 previously reported OA-associated SNPs. Methods: A case-control study design was utilized in this study. Patients undergoing total hip/knee joint replacements due to severe OA were collected as cases. A group of healthy individuals with no evidence of OA was used as control. 105 SNPs were genotyped either by Sequenom iPLEX Gold method or Illumina GWAS genotyping platform. The cross-reference was performed on both methods in a subset of samples for genotyping quality control. A logistic regression model was used to test for associations between the SNPs and OA. Results: A total of 126 cases and 348 healthy controls were included in the final analysis. OA Patients were on average 9 years older than healthy controls (p<0.0001), but there was no difference in BMI. We were unable to replicate the previously reported associations. Two SNPs, rs2294995 (COL9A3), and rs1049007 (BMP2) showed an association with p<0.05, but the significance did not survive the Bonferroni multiple testing correction. Conclusion: A lack of replication might be due to study design, complexity of OA, method of OA ascertainment, populations studied, or false positives in the original publications. A study with larger sample is needed to confirm the two possible SNPs with OA.
Authors and Affiliations
Guangju Zhai
Keywords
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- EP ID EP206877
- DOI 10.13188/2334-2846.1000009
- Views 124
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