Adjustment of Cell-Type Composition Minimizes Systematic Bias in Blood DNA Methylation Profiles Derived by DNA Collection Protocols

PloS One
Yuh ShiwaAtsushi Shimizu

Abstract

Differences in DNA collection protocols may be a potential confounder in epigenome-wide association studies (EWAS) using a large number of blood specimens from multiple biobanks and/or cohorts. Here we show that pre-analytical procedures involved in DNA collection can induce systematic bias in the DNA methylation profiles of blood cells that can be adjusted by cell-type composition variables. In Experiment 1, whole blood from 16 volunteers was collected to examine the effect of a 24 h storage period at 4°C on DNA methylation profiles as measured using the Infinium HumanMethylation450 BeadChip array. Our statistical analysis showed that the P-value distribution of more than 450,000 CpG sites was similar to the theoretical distribution (in quantile-quantile plot, λ = 1.03) when comparing two control replicates, which was remarkably deviated from the theoretical distribution (λ = 1.50) when comparing control and storage conditions. We then considered cell-type composition as a possible cause of the observed bias in DNA methylation profiles and found that the bias associated with the cold storage condition was largely decreased (λ adjusted = 1.14) by taking into account a cell-type composition variable. As such, we compared four re...Continue Reading

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Citations

May 20, 2016·Scientific Reports·Ryohei FurukawaAtsushi Shimizu
Sep 6, 2017·Omics : a Journal of Integrative Biology·Jae-Eun Lee, Young-Youl Kim
Dec 13, 2018·PloS One·Hanne Sagsveen HjorthaugMonica Cheng Munthe-Kaas
Feb 20, 2018·Clinical Epigenetics·Kira GroenJeannette Lechner-Scott
Sep 12, 2020·Environment International·Xueling LuJana V van Vliet-Ostaptchouk

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Methods Mentioned

BETA
blood collection
Assay
blood
methylation
chip
chips
FACS
flow cytometry
electrophoresis
between

Software Mentioned

minfi
EWAS
Illumina GenomeStudio
Bioconductor minfi package
R
CPACOR

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