Novel region discovery method for Infinium 450K DNA methylation data reveals changes associated with aging in muscle and neuronal pathways
Version of Record online: 22 OCT 2013
© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 13, Issue 1, pages 142–155, February 2014
How to Cite
Ong, M.-L. and Holbrook, J. D. (2014), Novel region discovery method for Infinium 450K DNA methylation data reveals changes associated with aging in muscle and neuronal pathways. Aging Cell, 13: 142–155. doi: 10.1111/acel.12159
- Issue online: 16 JAN 2014
- Version of Record online: 22 OCT 2013
- Accepted manuscript online: 23 SEP 2013 03:45AM EST
- Manuscript Accepted: 31 AUG 2013
We describe a methodology for detecting differentially methylated regions (DMRs) and variably methylated regions (VMRs), in data from Infinium 450K arrays that are very widely used in epigenetic studies. Region detection is more specific than single CpG analysis as it increases the extent of common findings between studies, and is more powerful as it reduces the multiple testing problem inherent in epigenetic whole-genome association studies (EWAS). In addition, results driven by single erroneous probes are removed. We have used multiple publicly available Infinium 450K data sets to generate a consensus list of DMRs for age, supporting the hypothesis that aging is associated with specific epigenetic modifications. The consensus aging DMRs are significantly enriched for muscle biogenesis pathways. We find a massive increase in VMRs with age and in regions of the genome associated with open chromatin and neurotransmission. Old age VMRs are significantly enriched for neurotransmission pathways. EWAS studies should investigate the role of this interindividual variation in DNA methylation, in the age-associated diseases of sarcopenia and dementia.