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Methylation quantitative trait locus analysis of osteoarthritis links epigenetics with genetic risk.

Rushton MD, Reynard LN, Young DA, Shepherd C, Aubourg G, Gee F, Darlay R, Deehan D, Cordell HJ, Loughlin J - Hum. Mol. Genet. (2015)

Bottom Line: Well-powered genetic studies have identified a number of DNA polymorphisms that are associated with OA susceptibility.We investigated potential genotype-methylation correlations within a 1.0-1.5 Mb region surrounding each of 16 OA-associated single-nucleotide polymorphisms (SNPs) in 99 cartilage samples and identified four that function as meQTLs.These observations suggest that OA susceptibility loci regulate the level of DNA methylation in cis and provide a mechanistic explanation as to how these loci impact upon OA susceptibility, further increasing our understanding of the role of genetics and epigenetics in this common disease.

View Article: PubMed Central - PubMed

Affiliation: Musculoskeletal Research Group, Institute of Cellular Medicine and.

No MeSH data available.


Related in: MedlinePlus

Replication of the association between rs6976 and DNA methylation at cg18099408. (A–C) Plots show the association between genotype at rs6976 and the methylation levels at three CpGs measured by the pyrosequencing assay; (A) the discovery CpG cg18099408, (B) the CpG site located 5 bp downstream of cg18099408 and (C) the CpG site located 9 bp downstream of cg18099408. Data are shown for the 40 OA samples analysed. P-value was calculated using a Kruskal–Wallis test and was Bonferroni-corrected for multiple testing. Horizontal line represents the mean.
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DDV433F4: Replication of the association between rs6976 and DNA methylation at cg18099408. (A–C) Plots show the association between genotype at rs6976 and the methylation levels at three CpGs measured by the pyrosequencing assay; (A) the discovery CpG cg18099408, (B) the CpG site located 5 bp downstream of cg18099408 and (C) the CpG site located 9 bp downstream of cg18099408. Data are shown for the 40 OA samples analysed. P-value was calculated using a Kruskal–Wallis test and was Bonferroni-corrected for multiple testing. Horizontal line represents the mean.

Mentions: The GLT8D1 rs6976 discovery CpG site cg18099408 replicated in the cohort of 40 OA patients in the same direction as in the discovery cohort (P = 0.0029; Fig. 4A). Two additional CpG sites located 5 and 9 bp downstream from cg18099408 were captured by the pyrosequencing assay; these CpG sites also demonstrated significant correlation between rs6976 genotype and methylation, and in the same direction as cg18099408 (Fig. 4B and C).Figure 4.


Methylation quantitative trait locus analysis of osteoarthritis links epigenetics with genetic risk.

Rushton MD, Reynard LN, Young DA, Shepherd C, Aubourg G, Gee F, Darlay R, Deehan D, Cordell HJ, Loughlin J - Hum. Mol. Genet. (2015)

Replication of the association between rs6976 and DNA methylation at cg18099408. (A–C) Plots show the association between genotype at rs6976 and the methylation levels at three CpGs measured by the pyrosequencing assay; (A) the discovery CpG cg18099408, (B) the CpG site located 5 bp downstream of cg18099408 and (C) the CpG site located 9 bp downstream of cg18099408. Data are shown for the 40 OA samples analysed. P-value was calculated using a Kruskal–Wallis test and was Bonferroni-corrected for multiple testing. Horizontal line represents the mean.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664171&req=5

DDV433F4: Replication of the association between rs6976 and DNA methylation at cg18099408. (A–C) Plots show the association between genotype at rs6976 and the methylation levels at three CpGs measured by the pyrosequencing assay; (A) the discovery CpG cg18099408, (B) the CpG site located 5 bp downstream of cg18099408 and (C) the CpG site located 9 bp downstream of cg18099408. Data are shown for the 40 OA samples analysed. P-value was calculated using a Kruskal–Wallis test and was Bonferroni-corrected for multiple testing. Horizontal line represents the mean.
Mentions: The GLT8D1 rs6976 discovery CpG site cg18099408 replicated in the cohort of 40 OA patients in the same direction as in the discovery cohort (P = 0.0029; Fig. 4A). Two additional CpG sites located 5 and 9 bp downstream from cg18099408 were captured by the pyrosequencing assay; these CpG sites also demonstrated significant correlation between rs6976 genotype and methylation, and in the same direction as cg18099408 (Fig. 4B and C).Figure 4.

Bottom Line: Well-powered genetic studies have identified a number of DNA polymorphisms that are associated with OA susceptibility.We investigated potential genotype-methylation correlations within a 1.0-1.5 Mb region surrounding each of 16 OA-associated single-nucleotide polymorphisms (SNPs) in 99 cartilage samples and identified four that function as meQTLs.These observations suggest that OA susceptibility loci regulate the level of DNA methylation in cis and provide a mechanistic explanation as to how these loci impact upon OA susceptibility, further increasing our understanding of the role of genetics and epigenetics in this common disease.

View Article: PubMed Central - PubMed

Affiliation: Musculoskeletal Research Group, Institute of Cellular Medicine and.

No MeSH data available.


Related in: MedlinePlus