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Reliability of DNA methylation measures from dried blood spots and mononuclear cells using the HumanMethylation450k BeadArray


Dugue, P-A and English, DR and MacInnis, RJ and Jung, C-H and Bassett, JK and Fitzgerald, LM and Wong, EM and Joo, JE and Hopper, JL and Southey, MC and Giles, GG and Milne, RL, Reliability of DNA methylation measures from dried blood spots and mononuclear cells using the HumanMethylation450k BeadArray, Scientific Reports, 6 Article 30317. ISSN 2045-2322 (2016) [Refereed Article]


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Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1038/srep30317


The reliability of methylation measures from the widely used HumanMethylation450 (HM450K) microarray has not been assessed for DNA from dried blood spots (DBS) or peripheral blood mononuclear cells (PBMC), nor for combined data from different studies. Repeated HM450K methylation measures in DNA from DBS and PBMC samples were available from participants in six case-control studies nested within the Melbourne Collaborative Cohort Study. Reliability was assessed for individual CpGs by calculating the intraclass correlation coefficient (ICC) based on technical replicates (samples repeated in a single study; 126 PBMC, 136 DBS) and study duplicates (samples repeated across studies; 280 PBMC, 769 DBS) using mixed-effects models. Reliability based on technical replicates was moderate for PBMC (median ICC = 0.42), but lower for DBS (median ICC = 0.20). Study duplicates gave lower ICCs than technical replicates. CpGs that were either highly methylated or unmethylated generally had lower ICCs, which appeared to be mostly related to their lower variability. The ICCs for global methylation measures were high, typically greater than 0.70. The reliability of methylation measures determined by the HM450K microarray is wide-ranging and depends primarily on the variability in methylation at individual CpG sites. The power of association studies is low for a substantial proportion of CpGs in the HM450K assay.

Item Details

Item Type:Refereed Article
Keywords:DNA methylation
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Epigenetics (incl. genome methylation and epigenomics)
Objective Division:Health
Objective Group:Evaluation of health and support services
Objective Field:Evaluation of health and support services not elsewhere classified
UTAS Author:Fitzgerald, LM (Dr Liesel Fitzgerald)
ID Code:110621
Year Published:2016
Web of Science® Times Cited:35
Deposited By:Menzies Institute for Medical Research
Deposited On:2016-08-05
Last Modified:2017-11-07
Downloads:183 View Download Statistics

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