Peripheral DNA Methylation, Cognitive Decline and Brain Aging: Pilot Findings from The Whitehall II Imaging Study

Abstract

Aim: The present study investigated the link between peripheral DNA methylation (DNAm), cognitive impairment and brain aging. Methods: We tested the association between blood genome-wide DNAm profiles using the Illumina 450K arrays, cognitive dysfunction and brain MRI measures in selected participants of the Whitehall II imaging sub-study. Results: Eight differentially methylated regions were associated with cognitive impairment. Accelerated aging based on the Hannum epigenetic clock was associated with mean diffusivity and global fractional anisotropy. We also identified modules of co-methylated loci associated with white matter hyperintensities. These co-methylation modules were enriched among pathways relevant to β-amyloid processing and glutamatergic signaling. Conclusion: Our data support the notion that blood DNAm changes may have utility as a biomarker for cognitive dysfunction and brain aging.

Keywords::

• brain aging
• DNA methylation
• epigenetic clock
• MCI
• mild cognitive impairment
• MRI
• peripheral biomarker

Supplementary data

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www.tandfonline.com/doi/full/10.2217/epi-2017-0132

Acknowledgements

The authors thank the Whitehall II cohort participants for their time.

Financial & competing interests disclosure

The study was funded by the National Institute for Health Research (NIHR) Academic Clinical Fellowship programme (L Chouliaras), the Oxfordshire Health Services Research Committee (L Chouliaras), the Oxford University Clinical Academic Graduate School (L Chouliaras), the UK Medical Research Council (MRC; G1001354; K P Ebmeier; K013351; M Kivimäki)  and also as part of the Joint Programme – Neurodegenerative Disease Research grant for the EPI-AD consortium (MR/N027973/1; K Lunnon, E Pishva), the Gordon Edward Small’s Charitable Trust (SC008962; K P Ebmeier) and the HDH Wills 1965 charitable trust (charity No: 1117747; K P Ebmeier). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The study was funded by the National Institute for Health Research (NIHR) Academic Clinical Fellowship programme (L Chouliaras), the Oxfordshire Health Services Research Committee (L Chouliaras), the Oxford University Clinical Academic Graduate School (L Chouliaras), the UK Medical Research Council (MRC; G1001354; K P Ebmeier; K013351; M Kivimäki)  and also as part of the Joint Programme – Neurodegenerative Disease Research grant for the EPI-AD consortium (MR/N027973/1; K Lunnon, E Pishva), the Gordon Edward Small’s Charitable Trust (SC008962; K P Ebmeier) and the HDH Wills 1965 charitable trust (charity No: 1117747; K P Ebmeier). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.