Journal
EPIGENOMICS
Volume 9, Issue 8, Pages 1143-1150Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/epi-2017-0032
Keywords
biomarkers; cell fate; cellular heterogeneity; DNA methylation; DoHAD; epigenetic epidemiology; epigenetics; EWAS; methWAS
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Funding
- Abbott Nutrition
- Nestec
- National Institute for Health Research through the NIHR Southampton Biomedical Research Centre
- NHMRC Fellowship [1053384]
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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.
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