Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility.

Methylation of cytosines at CpG sites is a common epigenetic DNA modification that can be measured by a large number of methods, now even in a genome-wide manner for hundreds of thousands of sites. The application of DNA methylation analysis is becoming widely popular in complex disorders, for examp...

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Autores principales:	Lovisa E Reinius, Nathalie Acevedo, Maaike Joerink, Göran Pershagen, Sven-Erik Dahlén, Dario Greco, Cilla Söderhäll, Annika Scheynius, Juha Kere
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5d41c18250b8483aac0c5924dcda9b6e
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spelling	oai:doaj.org-article:5d41c18250b8483aac0c5924dcda9b6e2021-11-18T07:11:09ZDifferential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility.1932-620310.1371/journal.pone.0041361https://doaj.org/article/5d41c18250b8483aac0c5924dcda9b6e2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22848472/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Methylation of cytosines at CpG sites is a common epigenetic DNA modification that can be measured by a large number of methods, now even in a genome-wide manner for hundreds of thousands of sites. The application of DNA methylation analysis is becoming widely popular in complex disorders, for example, to understand part of the "missing heritability". The DNA samples most readily available for methylation studies are derived from whole blood. However, blood consists of many functionally and developmentally distinct cell populations in varying proportions. We studied whether such variation might affect the interpretation of methylation studies based on whole blood DNA. We found in healthy male blood donors there is important variation in the methylation profiles of whole blood, mononuclear cells, granulocytes, and cells from seven selected purified lineages. CpG methylation between mononuclear cells and granulocytes differed for 22% of the 8252 probes covering the selected 343 genes implicated in immune-related disorders by genome-wide association studies, and at least one probe was differentially methylated for 85% of the genes, indicating that whole blood methylation results might be unintelligible. For individual genes, even if the overall methylation patterns might appear similar, a few CpG sites in the regulatory regions may have opposite methylation patterns (i.e., hypo/hyper) in the main blood cell types. We conclude that interpretation of whole blood methylation profiles should be performed with great caution and for any differences implicated in a disorder, the differences resulting from varying proportions of white blood cell types should be considered.Lovisa E ReiniusNathalie AcevedoMaaike JoerinkGöran PershagenSven-Erik DahlénDario GrecoCilla SöderhällAnnika ScheyniusJuha KerePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e41361 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lovisa E Reinius Nathalie Acevedo Maaike Joerink Göran Pershagen Sven-Erik Dahlén Dario Greco Cilla Söderhäll Annika Scheynius Juha Kere Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility.
description	Methylation of cytosines at CpG sites is a common epigenetic DNA modification that can be measured by a large number of methods, now even in a genome-wide manner for hundreds of thousands of sites. The application of DNA methylation analysis is becoming widely popular in complex disorders, for example, to understand part of the "missing heritability". The DNA samples most readily available for methylation studies are derived from whole blood. However, blood consists of many functionally and developmentally distinct cell populations in varying proportions. We studied whether such variation might affect the interpretation of methylation studies based on whole blood DNA. We found in healthy male blood donors there is important variation in the methylation profiles of whole blood, mononuclear cells, granulocytes, and cells from seven selected purified lineages. CpG methylation between mononuclear cells and granulocytes differed for 22% of the 8252 probes covering the selected 343 genes implicated in immune-related disorders by genome-wide association studies, and at least one probe was differentially methylated for 85% of the genes, indicating that whole blood methylation results might be unintelligible. For individual genes, even if the overall methylation patterns might appear similar, a few CpG sites in the regulatory regions may have opposite methylation patterns (i.e., hypo/hyper) in the main blood cell types. We conclude that interpretation of whole blood methylation profiles should be performed with great caution and for any differences implicated in a disorder, the differences resulting from varying proportions of white blood cell types should be considered.
format	article
author	Lovisa E Reinius Nathalie Acevedo Maaike Joerink Göran Pershagen Sven-Erik Dahlén Dario Greco Cilla Söderhäll Annika Scheynius Juha Kere
author_facet	Lovisa E Reinius Nathalie Acevedo Maaike Joerink Göran Pershagen Sven-Erik Dahlén Dario Greco Cilla Söderhäll Annika Scheynius Juha Kere
author_sort	Lovisa E Reinius
title	Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility.
title_short	Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility.
title_full	Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility.
title_fullStr	Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility.
title_full_unstemmed	Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility.
title_sort	differential dna methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/5d41c18250b8483aac0c5924dcda9b6e
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Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility.

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