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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

Genotype at rs6976 correlates with the methylation levels at three CpG sites within the gene body of STAB1. (A) The plot shows the association between rs6976 and the methylation levels of CpG probes that are present within the LD block. The x-axis represents the genomic position of the CpG probes, and the y-axis represents the Benjamini–Hochberg corrected −log10P-value of the correlation between rs6976 genotype and β-value at each CpG probe. Each open circle represents a single CpG probe, and the three significant associations are labelled (cg15147215 and cg18591801 have the same P-value and on the x-axis scale used are represented by a single open circle). The LD block is indicated by the vertical dotted lines and the location of rs6976 by the bold dashed line. The genes within the region analysed are indicated below the association plot, with the gene direction indicated by arrows. (B) The association between genotype at rs6976 and methylation levels at the three significant CpG probes. Due to the significant methylation differences at these CpGs between OA and NOF samples, data are shown only for the 80 OA samples from the discovery cohort of 99 samples. The level of methylation at the CpG probes is shown as the β-value. Horizontal line represents the mean.
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DDV433F1: Genotype at rs6976 correlates with the methylation levels at three CpG sites within the gene body of STAB1. (A) The plot shows the association between rs6976 and the methylation levels of CpG probes that are present within the LD block. The x-axis represents the genomic position of the CpG probes, and the y-axis represents the Benjamini–Hochberg corrected −log10P-value of the correlation between rs6976 genotype and β-value at each CpG probe. Each open circle represents a single CpG probe, and the three significant associations are labelled (cg15147215 and cg18591801 have the same P-value and on the x-axis scale used are represented by a single open circle). The LD block is indicated by the vertical dotted lines and the location of rs6976 by the bold dashed line. The genes within the region analysed are indicated below the association plot, with the gene direction indicated by arrows. (B) The association between genotype at rs6976 and methylation levels at the three significant CpG probes. Due to the significant methylation differences at these CpGs between OA and NOF samples, data are shown only for the 80 OA samples from the discovery cohort of 99 samples. The level of methylation at the CpG probes is shown as the β-value. Horizontal line represents the mean.

Mentions: Genotype at GLT8D1 SNP rs6976 correlated with the methylation of three CpGs located ∼31.5 kb upstream of the LD block and ∼170 kb from the SNP: cg18099408, cg15147215 and cg18591801. All three CpGs are within the gene body of STAB1 (Fig. 1A), and for each CpG, the OA-associated T allele of rs6976 correlated with lower methylation (Fig. 1B; data for the OA patients only shown). Significant correlations were seen when all of the patient samples were combined (OA knee, OA hip and NOF) as well as in OA samples alone (Table 2).Figure 1.


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)

Genotype at rs6976 correlates with the methylation levels at three CpG sites within the gene body of STAB1. (A) The plot shows the association between rs6976 and the methylation levels of CpG probes that are present within the LD block. The x-axis represents the genomic position of the CpG probes, and the y-axis represents the Benjamini–Hochberg corrected −log10P-value of the correlation between rs6976 genotype and β-value at each CpG probe. Each open circle represents a single CpG probe, and the three significant associations are labelled (cg15147215 and cg18591801 have the same P-value and on the x-axis scale used are represented by a single open circle). The LD block is indicated by the vertical dotted lines and the location of rs6976 by the bold dashed line. The genes within the region analysed are indicated below the association plot, with the gene direction indicated by arrows. (B) The association between genotype at rs6976 and methylation levels at the three significant CpG probes. Due to the significant methylation differences at these CpGs between OA and NOF samples, data are shown only for the 80 OA samples from the discovery cohort of 99 samples. The level of methylation at the CpG probes is shown as the β-value. Horizontal line represents the mean.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

DDV433F1: Genotype at rs6976 correlates with the methylation levels at three CpG sites within the gene body of STAB1. (A) The plot shows the association between rs6976 and the methylation levels of CpG probes that are present within the LD block. The x-axis represents the genomic position of the CpG probes, and the y-axis represents the Benjamini–Hochberg corrected −log10P-value of the correlation between rs6976 genotype and β-value at each CpG probe. Each open circle represents a single CpG probe, and the three significant associations are labelled (cg15147215 and cg18591801 have the same P-value and on the x-axis scale used are represented by a single open circle). The LD block is indicated by the vertical dotted lines and the location of rs6976 by the bold dashed line. The genes within the region analysed are indicated below the association plot, with the gene direction indicated by arrows. (B) The association between genotype at rs6976 and methylation levels at the three significant CpG probes. Due to the significant methylation differences at these CpGs between OA and NOF samples, data are shown only for the 80 OA samples from the discovery cohort of 99 samples. The level of methylation at the CpG probes is shown as the β-value. Horizontal line represents the mean.
Mentions: Genotype at GLT8D1 SNP rs6976 correlated with the methylation of three CpGs located ∼31.5 kb upstream of the LD block and ∼170 kb from the SNP: cg18099408, cg15147215 and cg18591801. All three CpGs are within the gene body of STAB1 (Fig. 1A), and for each CpG, the OA-associated T allele of rs6976 correlated with lower methylation (Fig. 1B; data for the OA patients only shown). Significant correlations were seen when all of the patient samples were combined (OA knee, OA hip and NOF) as well as in OA samples alone (Table 2).Figure 1.

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