Is cellular heterogeneity merely a confounder to be removed from epigenome-wide association studies?
Is cellular heterogeneity merely a confounder to be removed from epigenome-wide association studies?
Excitement about DNA methylation biomarkers has been tempered by a growing appreciation of the complex causal relations with cell fate. Inter-sample 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 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 aetiology including aspects of causation.
Holbrook, Joanna D
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Lillycrop, Karen
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Barton, Sheila
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July 2017
Holbrook, Joanna D
69989b79-2710-4f12-946e-c6214e1b6513
Lillycrop, Karen
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Barton, Sheila
4f674382-ca0b-44ad-9670-e71a0b134ef0
Holbrook, Joanna D, Lillycrop, Karen and Barton, Sheila
(2017)
Is cellular heterogeneity merely a confounder to be removed from epigenome-wide association studies?
Epigenomics, 9 (8).
(doi:10.2217/epi-2017-0032).
Abstract
Excitement about DNA methylation biomarkers has been tempered by a growing appreciation of the complex causal relations with cell fate. Inter-sample 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 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 aetiology including aspects of causation.
Text
Is cellular heterogenity a confounder to remove_accepted
- Accepted Manuscript
More information
Accepted/In Press date: 18 May 2017
e-pub ahead of print date: 27 July 2017
Published date: July 2017
Organisations:
Faculty of Natural and Environmental Sciences, MRC Lifecourse Epidemiology Unit, Human Development & Health, Centre for Biological Sciences
Identifiers
Local EPrints ID: 410238
URI: http://eprints.soton.ac.uk/id/eprint/410238
ISSN: 1750-1911
PURE UUID: 3f2a6b51-c4e8-4f31-bd93-1e51dc187857
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Date deposited: 06 Jun 2017 04:02
Last modified: 16 Mar 2024 05:22
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Author:
Joanna D Holbrook
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