Peripheral DNA methylation, cognitive decline and brain aging: pilot findings from the Whitehall II imaging study

Leonidas Chouliaras; Ehsan Pishva; Rita Haapakoski; Eniko Zsoldos; Abda Mahmood; Nicola Filippini; Joe Burrage; Jonathan Mill; Mika Kivimaki; Katie Lunnon; Klaus P. Ebmeier

doi:10.2217/epi-2017-0132

Peripheral DNA methylation, cognitive decline and brain aging: pilot findings from the Whitehall II imaging study

Leonidas Chouliaras^*, Ehsan Pishva, Rita Haapakoski, Eniko Zsoldos, Abda Mahmood, Nicola Filippini, Joe Burrage, Jonathan Mill, Mika Kivimaki, Katie Lunnon, Klaus P. Ebmeier

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 beta-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.

Original language	English
Pages (from-to)	585-595
Number of pages	11
Journal	Epigenomics
Volume	10
Issue number	5
DOIs	https://doi.org/10.2217/epi-2017-0132
Publication status	Published - 1 May 2018

Keywords

brain aging
DNA methylation
epigenetic clock
MCI
mild cognitive impairment
MRI
peripheral biomarker
MESSENGER-RNA EXPRESSION
ALZHEIMERS-DISEASE
INTRON 1
BLOOD
DEMENTIA
TREM2
AGE
DYSREGULATION
HIPPOCAMPUS
ENRICHMENT

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Cite this

@article{591966c8a1af4ec1bcb1e78df11eab87,

title = "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 beta-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.",

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author = "Leonidas Chouliaras and Ehsan Pishva and Rita Haapakoski and Eniko Zsoldos and Abda Mahmood and Nicola Filippini and Joe Burrage and Jonathan Mill and Mika Kivimaki and Katie Lunnon and Ebmeier, {Klaus P.}",

year = "2018",

month = may,

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doi = "10.2217/epi-2017-0132",

language = "English",

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T1 - Peripheral DNA methylation, cognitive decline and brain aging

T2 - pilot findings from the Whitehall II imaging study

AU - Chouliaras, Leonidas

AU - Pishva, Ehsan

AU - Haapakoski, Rita

AU - Zsoldos, Eniko

AU - Mahmood, Abda

AU - Filippini, Nicola

AU - Burrage, Joe

AU - Mill, Jonathan

AU - Kivimaki, Mika

AU - Lunnon, Katie

AU - Ebmeier, Klaus P.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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 beta-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.

AB - 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 beta-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.

KW - brain aging

KW - DNA methylation

KW - epigenetic clock

KW - MCI

KW - mild cognitive impairment

KW - MRI

KW - peripheral biomarker

KW - MESSENGER-RNA EXPRESSION

KW - ALZHEIMERS-DISEASE

KW - INTRON 1

KW - BLOOD

KW - DEMENTIA

KW - TREM2

KW - AGE

KW - DYSREGULATION

KW - HIPPOCAMPUS

KW - ENRICHMENT

U2 - 10.2217/epi-2017-0132

DO - 10.2217/epi-2017-0132

M3 - Article

C2 - 29692214

SN - 1750-1911

VL - 10

SP - 585

EP - 595

JO - Epigenomics

JF - Epigenomics

IS - 5

ER -