1,833
Views
0
CrossRef citations to date
0
Altmetric
Perspective

Is Cellular Heterogeneity Merely a Confounder to be Removed from Epigenome-Wide Association Studies?

, , , &
Pages 1143-1150 | Received 26 Feb 2017, Accepted 23 May 2017, Published online: 27 Jul 2017
 

Abstract

Excitement about DNA methylation biomarkers has been tempered by a growing appreciation of the complex causal relations with cell fate. Intersample differences in DNA methylation can be partitioned into those that are independent of cellular heterogeneity and those that are caused by differential mixtures of cell types. Generally, the field has assumed that the former are more likely to be causative of disease. The latter has been considered a likely consequence of disease and a confounder to be removed. We argue that the conceptual separation of these signals is artificial and not necessarily informative about causation. DNA methylation is a very sensitive measure of cell fate mix and therefore reveals much about underlying disease etiology including aspects of causation.

Financial & competing interests disclosure

KA Lillycrop, SJ Barton and JD Holbrook are part of an academic consortium that has received research funding from Abbott Nutrition and Nestec. JD Holbrook is supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Centre. R-C Huang is supported by NH&MRC Fellowship #1053384. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

KA Lillycrop, SJ Barton and JD Holbrook are part of an academic consortium that has received research funding from Abbott Nutrition and Nestec. JD Holbrook is supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Centre. R-C Huang is supported by NH&MRC Fellowship #1053384. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.