Novel region discovery method for Infinium 450K DNA methylation data reveals changes associated with aging in muscle and neuronal pathways

Aging Cell

Mei-Lyn Ong¹ 

[1] Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Brenner Centre for Molecular Medicine, Singapore, 117609, Singapore

关键词: aging;    epigenetics;    EWAS;    Infinium;    methylation;    sarcopenia;   

DOI  :  10.1111/acel.12159

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

CC BY   
© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.