Accounting for cellular heterogeneity is critical in epigenome-wide association studies

Andrew Jaffe, Rafael A. Irizarry

Research output: Contribution to journalArticle

Abstract

Background: Epigenome-wide association studies of human disease and other quantitative traits are becoming increasingly common. A series of papers reporting age-related changes in DNA methylation profiles in peripheral blood have already been published. However, blood is a heterogeneous collection of different cell types, each with a very different DNA methylation profile.Results: Using a statistical method that permits estimating the relative proportion of cell types from DNA methylation profiles, we examine data from five previously published studies, and find strong evidence of cell composition change across age in blood. We also demonstrate that, in these studies, cellular composition explains much of the observed variability in DNA methylation. Furthermore, we find high levels of confounding between age-related variability and cellular composition at the CpG level.Conclusions: Our findings underscore the importance of considering cell composition variability in epigenetic studies based on whole blood and other heterogeneous tissue sources. We also provide software for estimating and exploring this composition confounding for the Illumina 450k microarray.

Original languageEnglish (US)
Article numberR31
JournalGenome Biology
Volume15
Issue number2
DOIs
StatePublished - Feb 4 2014

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methylation
DNA methylation
DNA Methylation
blood
DNA
cells
Age Factors
quantitative traits
human diseases
Epigenomics
epigenetics
statistical analysis
Software
software

ASJC Scopus subject areas

  • Genetics
  • Cell Biology
  • Ecology, Evolution, Behavior and Systematics
  • Medicine(all)

Cite this

Accounting for cellular heterogeneity is critical in epigenome-wide association studies. / Jaffe, Andrew; Irizarry, Rafael A.

In: Genome Biology, Vol. 15, No. 2, R31, 04.02.2014.

Research output: Contribution to journalArticle

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