Estimation of blood cellular heterogeneity in newborns and children for epigenome-wide association studies

Environmental and Molecular Mutagenesis
Paul YousefiNina Holland

Abstract

Confounding by cellular heterogeneity has become a major concern for epigenome-wide association studies (EWAS) in peripheral blood samples from population and clinical studies. Adjusting for white blood cell percentage estimates produced by the minfi implementation of the Houseman algorithm (minfi) during statistical analysis is now an established method to account for this bias in adults. However, minfi has not been benchmarked against white blood cell counts in children that may differ substantially from the reference dataset used in its estimation. We compared estimates of white blood cell type percentages produced by two methods, minfi and differential cell count (DCC), in a birth cohort at two time points (birth and 12 years of age). We found that both minfi and DCC had similar trends as children aged, and neither count method differed by sex among newborns (P > 0.10). However, minfi estimates did not correlate well with DCC in samples from newborns (ρ = -0.05 for granulocytes; ρ = -0.03 for lymphocytes). In older children, correlation improved substantially (ρ = 0.77 for granulocytes; ρ = 0.75 for lymphocytes), likely due to increasing similarity with minfi's adult reference data as children aged. Our findings suggest tha...Continue Reading

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Citations

Mar 29, 2016·Epigenetics : Official Journal of the DNA Methylation Society·Kelly M BakulskiM Daniele Fallin
Apr 8, 2016·Epigenomics·Xinyi LinJoanna D Holbrook
Aug 6, 2016·Epigenetics : Official Journal of the DNA Methylation Society·Kristina GervinRobert Lyle
Oct 25, 2016·Epigenetics : Official Journal of the DNA Methylation Society·Andres CardenasMarie-France Hivert
Oct 13, 2017·International Journal of Epidemiology·Janine F FelixStephanie J London
Nov 11, 2015·BMC Genomics·Paul YousefiNina Holland
Mar 23, 2017·Epigenomics·Daniel P PotaczekJörg Tost
Nov 29, 2016·Clinical Epigenetics·Golareh AghaAndrea A Baccarelli
Apr 9, 2019·Environmental Epigenetics·Gwen TindulaNina Holland
May 31, 2017·Environmental and Molecular Mutagenesis·Olivia SolomonNina Holland
Feb 6, 2017·Epigenetics & Chromatin·Elior RahmaniEran Halperin
Oct 17, 2017·Annual Review of Psychology·Meaghan J JonesMichael S Kobor

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