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Discordance of DNA methylation variance between two accessible human tissues.

Jiang R, Jones MJ, Chen E, Neumann SM, Fraser HB, Miller GE, Kobor MS - Sci Rep (2015)

Bottom Line: Specifically we compared probe-wise DNA methylation variance, and how this variance related to demographic factors across the two tissues.Lastly, through exploratory association analysis, we found indication of differential association of BEC and PBMC with demographic variables.The work presented here offers insight into variability of DNA methylation between individuals and across tissues and helps guide decisions on the suitability of buccal epithelial or peripheral mononuclear cells for the biological questions explored by epigenetic studies in human populations.

View Article: PubMed Central - PubMed

Affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada.

ABSTRACT
Population epigenetic studies have been seeking to identify differences in DNA methylation between specific exposures, demographic factors, or diseases in accessible tissues, but relatively little is known about how inter-individual variability differs between these tissues. This study presents an analysis of DNA methylation differences between matched peripheral blood mononuclear cells (PMBCs) and buccal epithelial cells (BECs), the two most accessible tissues for population studies, in 998 promoter-located CpG sites. Specifically we compared probe-wise DNA methylation variance, and how this variance related to demographic factors across the two tissues. PBMCs had overall higher DNA methylation than BECs, and the two tissues tended to differ most at genomic regions of low CpG density. Furthermore, although both tissues showed appreciable probe-wise variability, the specific regions and magnitude of variability differed strongly between tissues. Lastly, through exploratory association analysis, we found indication of differential association of BEC and PBMC with demographic variables. The work presented here offers insight into variability of DNA methylation between individuals and across tissues and helps guide decisions on the suitability of buccal epithelial or peripheral mononuclear cells for the biological questions explored by epigenetic studies in human populations.

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Related in: MedlinePlus

DNA methylation variability was tissue specific.584 probes had PBMC variance that deviated <±20% from their corresponding BEC variance. 414 probes were found beyond the ±20% threshold, further demonstrating the variance discordance between BEC and PBMC.
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f4: DNA methylation variability was tissue specific.584 probes had PBMC variance that deviated <±20% from their corresponding BEC variance. 414 probes were found beyond the ±20% threshold, further demonstrating the variance discordance between BEC and PBMC.

Mentions: Taking advantage of our matched study design, we compared variability of sites between BEC and PBMC directly by calculating the variance for each probe, and determining equality of variance using Levene's test38. This site-by-site evaluation of variance equality showed that 346 (34.7%) loci did not have equitable variance across the two tissues (Levene test p-value <0.05). Of these loci, 144 showed larger BEC variance, and 202 showed larger PBMC variance. This is in contrast to the earlier analysis where we found more sites with large SD in BEC when examining each tissue separately. Plotting the variance of PBMC versus the variance of BEC, we obtained a Pearson's correlation coefficient of 0.26 (Fig. 4). By setting variance in BEC as a reference, we searched for probes for which the PBMC variance deviates more than ±20% from the BEC variance. Using this method we found 584 probes residing within the ±20% interval, and 414 probes outside the interval (Fig. 4). These observations indicated that variance was specific to the tissue; a probe that was highly variable in BEC would most likely not behave the same way in PBMC.


Discordance of DNA methylation variance between two accessible human tissues.

Jiang R, Jones MJ, Chen E, Neumann SM, Fraser HB, Miller GE, Kobor MS - Sci Rep (2015)

DNA methylation variability was tissue specific.584 probes had PBMC variance that deviated <±20% from their corresponding BEC variance. 414 probes were found beyond the ±20% threshold, further demonstrating the variance discordance between BEC and PBMC.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321176&req=5

f4: DNA methylation variability was tissue specific.584 probes had PBMC variance that deviated <±20% from their corresponding BEC variance. 414 probes were found beyond the ±20% threshold, further demonstrating the variance discordance between BEC and PBMC.
Mentions: Taking advantage of our matched study design, we compared variability of sites between BEC and PBMC directly by calculating the variance for each probe, and determining equality of variance using Levene's test38. This site-by-site evaluation of variance equality showed that 346 (34.7%) loci did not have equitable variance across the two tissues (Levene test p-value <0.05). Of these loci, 144 showed larger BEC variance, and 202 showed larger PBMC variance. This is in contrast to the earlier analysis where we found more sites with large SD in BEC when examining each tissue separately. Plotting the variance of PBMC versus the variance of BEC, we obtained a Pearson's correlation coefficient of 0.26 (Fig. 4). By setting variance in BEC as a reference, we searched for probes for which the PBMC variance deviates more than ±20% from the BEC variance. Using this method we found 584 probes residing within the ±20% interval, and 414 probes outside the interval (Fig. 4). These observations indicated that variance was specific to the tissue; a probe that was highly variable in BEC would most likely not behave the same way in PBMC.

Bottom Line: Specifically we compared probe-wise DNA methylation variance, and how this variance related to demographic factors across the two tissues.Lastly, through exploratory association analysis, we found indication of differential association of BEC and PBMC with demographic variables.The work presented here offers insight into variability of DNA methylation between individuals and across tissues and helps guide decisions on the suitability of buccal epithelial or peripheral mononuclear cells for the biological questions explored by epigenetic studies in human populations.

View Article: PubMed Central - PubMed

Affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada.

ABSTRACT
Population epigenetic studies have been seeking to identify differences in DNA methylation between specific exposures, demographic factors, or diseases in accessible tissues, but relatively little is known about how inter-individual variability differs between these tissues. This study presents an analysis of DNA methylation differences between matched peripheral blood mononuclear cells (PMBCs) and buccal epithelial cells (BECs), the two most accessible tissues for population studies, in 998 promoter-located CpG sites. Specifically we compared probe-wise DNA methylation variance, and how this variance related to demographic factors across the two tissues. PBMCs had overall higher DNA methylation than BECs, and the two tissues tended to differ most at genomic regions of low CpG density. Furthermore, although both tissues showed appreciable probe-wise variability, the specific regions and magnitude of variability differed strongly between tissues. Lastly, through exploratory association analysis, we found indication of differential association of BEC and PBMC with demographic variables. The work presented here offers insight into variability of DNA methylation between individuals and across tissues and helps guide decisions on the suitability of buccal epithelial or peripheral mononuclear cells for the biological questions explored by epigenetic studies in human populations.

Show MeSH
Related in: MedlinePlus