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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 (A) ALDH1A2 rs3204689-cg12031962 and (B) UQCC/GDF5 rs143383-cg14752227 meQTLs. For rs3204689, data are shown for the discovery CpG, cg12031962 (left) and an additional CpG located 12 bp downstream (right). For rs143383, data are shown for the discovery CpG, cg14752227 (left) and an additional CpG captured by the assay located 38 bp downstream of cg14752227 (right). For both SNPs, data are shown for the 45 samples studied; 40 OA and 5 NOF. 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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DDV433F6: Replication of the (A) ALDH1A2 rs3204689-cg12031962 and (B) UQCC/GDF5 rs143383-cg14752227 meQTLs. For rs3204689, data are shown for the discovery CpG, cg12031962 (left) and an additional CpG located 12 bp downstream (right). For rs143383, data are shown for the discovery CpG, cg14752227 (left) and an additional CpG captured by the assay located 38 bp downstream of cg14752227 (right). For both SNPs, data are shown for the 45 samples studied; 40 OA and 5 NOF. P-value was calculated using a Kruskal–Wallis test and was Bonferroni-corrected for multiple testing. Horizontal line represents the mean.

Mentions: The effect of the ALDH1A2 rs3204689 SNP genotype on methylation of the cg12031962 CpG was also observed in the additional cohort of 45 cartilage samples (P < 0.0001; Fig. 6A, left graph). Additionally, the OA-associated C allele of rs3204689 correlated with reduced methylation of another CpG site captured by the assay that is located 12 bp downstream of cg12031962 (P = 0.0002; Fig. 6A, right graph).Figure 6.


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 (A) ALDH1A2 rs3204689-cg12031962 and (B) UQCC/GDF5 rs143383-cg14752227 meQTLs. For rs3204689, data are shown for the discovery CpG, cg12031962 (left) and an additional CpG located 12 bp downstream (right). For rs143383, data are shown for the discovery CpG, cg14752227 (left) and an additional CpG captured by the assay located 38 bp downstream of cg14752227 (right). For both SNPs, data are shown for the 45 samples studied; 40 OA and 5 NOF. 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

DDV433F6: Replication of the (A) ALDH1A2 rs3204689-cg12031962 and (B) UQCC/GDF5 rs143383-cg14752227 meQTLs. For rs3204689, data are shown for the discovery CpG, cg12031962 (left) and an additional CpG located 12 bp downstream (right). For rs143383, data are shown for the discovery CpG, cg14752227 (left) and an additional CpG captured by the assay located 38 bp downstream of cg14752227 (right). For both SNPs, data are shown for the 45 samples studied; 40 OA and 5 NOF. P-value was calculated using a Kruskal–Wallis test and was Bonferroni-corrected for multiple testing. Horizontal line represents the mean.
Mentions: The effect of the ALDH1A2 rs3204689 SNP genotype on methylation of the cg12031962 CpG was also observed in the additional cohort of 45 cartilage samples (P < 0.0001; Fig. 6A, left graph). Additionally, the OA-associated C allele of rs3204689 correlated with reduced methylation of another CpG site captured by the assay that is located 12 bp downstream of cg12031962 (P = 0.0002; Fig. 6A, right graph).Figure 6.

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