Limits...
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

eQTL and methylation–expression correlations for ALDH1A2. (A) ALDH1A2 expression in cartilage from 29 OA knee patients stratified by genotype at rs3204689. Horizontal line represents the mean. (B) ALDH1A2 expression plotted against methylation at cg12031962. r represents the Spearman rank coefficient and the P-value was calculated using a Kruskal–Wallis test and was Bonferroni-corrected for multiple testing.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4664171&req=5

DDV433F7: eQTL and methylation–expression correlations for ALDH1A2. (A) ALDH1A2 expression in cartilage from 29 OA knee patients stratified by genotype at rs3204689. Horizontal line represents the mean. (B) ALDH1A2 expression plotted against methylation at cg12031962. r represents the Spearman rank coefficient and the P-value was calculated using a Kruskal–Wallis test and was Bonferroni-corrected for multiple testing.

Mentions: None of the genes showed a significant correlation (P < 0.05; Spearman correlation) between gene expression and methylation, or between expression and genotype (Fig. 7; Supplementary Material, Figs S2 and S3). We did, however, observe a non-significant trend between ALDH1A2 expression and genotype at rs3204689 (P = 0.088; Fig. 7A), with the risk-conferring C allele correlating with reduced expression; this fits with the previous eQTL analysis of this locus in OA cartilage (13). There was also a non-significant positive correlation between ALDH1A2 expression and cg12031962 methylation in OA knee cartilage (Fig. 7B).Figure 7.


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)

eQTL and methylation–expression correlations for ALDH1A2. (A) ALDH1A2 expression in cartilage from 29 OA knee patients stratified by genotype at rs3204689. Horizontal line represents the mean. (B) ALDH1A2 expression plotted against methylation at cg12031962. r represents the Spearman rank coefficient and the P-value was calculated using a Kruskal–Wallis test and was Bonferroni-corrected for multiple testing.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

DDV433F7: eQTL and methylation–expression correlations for ALDH1A2. (A) ALDH1A2 expression in cartilage from 29 OA knee patients stratified by genotype at rs3204689. Horizontal line represents the mean. (B) ALDH1A2 expression plotted against methylation at cg12031962. r represents the Spearman rank coefficient and the P-value was calculated using a Kruskal–Wallis test and was Bonferroni-corrected for multiple testing.
Mentions: None of the genes showed a significant correlation (P < 0.05; Spearman correlation) between gene expression and methylation, or between expression and genotype (Fig. 7; Supplementary Material, Figs S2 and S3). We did, however, observe a non-significant trend between ALDH1A2 expression and genotype at rs3204689 (P = 0.088; Fig. 7A), with the risk-conferring C allele correlating with reduced expression; this fits with the previous eQTL analysis of this locus in OA cartilage (13). There was also a non-significant positive correlation between ALDH1A2 expression and cg12031962 methylation in OA knee cartilage (Fig. 7B).Figure 7.

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