This article is part of a special issue on epigenomics.

Open Access Highly Accessed Research

Aging effects on DNA methylation modules in human brain and blood tissue

Steve Horvath12*, Yafeng Zhang2, Peter Langfelder1, René S Kahn3, Marco PM Boks3, Kristel van Eijk34, Leonard H van den Berg5 and Roel A Ophoff26

Author affiliations

1 Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA

2 Department of Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA

3 Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands

4 Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands

5 Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands

6 UCLA Center for Neurobehavioral Genetics, Semel Institute of Neuroscience and Human Behavioral, School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA

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Citation and License

Genome Biology 2012, 13:R97  doi:10.1186/gb-2012-13-10-r97

Published: 3 October 2012

Abstract

Background

Several recent studies reported aging effects on DNA methylation levels of individual CpG dinucleotides. But it is not yet known whether aging-related consensus modules, in the form of clusters of correlated CpG markers, can be found that are present in multiple human tissues. Such a module could facilitate the understanding of aging effects on multiple tissues.

Results

We therefore employed weighted correlation network analysis of 2,442 Illumina DNA methylation arrays from brain and blood tissues, which enabled the identification of an age-related co-methylation module. Module preservation analysis confirmed that this module can also be found in diverse independent data sets. Biological evaluation showed that module membership is associated with Polycomb group target occupancy counts, CpG island status and autosomal chromosome location. Functional enrichment analysis revealed that the aging-related consensus module comprises genes that are involved in nervous system development, neuron differentiation and neurogenesis, and that it contains promoter CpGs of genes known to be down-regulated in early Alzheimer's disease. A comparison with a standard, non-module based meta-analysis revealed that selecting CpGs based on module membership leads to significantly increased gene ontology enrichment, thus demonstrating that studying aging effects via consensus network analysis enhances the biological insights gained.

Conclusions

Overall, our analysis revealed a robustly defined age-related co-methylation module that is present in multiple human tissues, including blood and brain. We conclude that blood is a promising surrogate for brain tissue when studying the effects of age on DNA methylation profiles.