Epigenome-wide analyses identify DNA methylation signatures of dementia risk.
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ABSTRACT: Introduction
Dementia pathogenesis begins years before clinical symptom onset, necessitating the understanding of premorbid risk mechanisms. Here we investigated potential pathogenic mechanisms by assessing DNA methylation associations with dementia risk factors in Alzheimer's disease (AD)-free participants.Methods
Associations between dementia risk measures (family history, AD genetic risk score [GRS], and dementia risk scores [combining lifestyle, demographic, and genetic factors]) and whole-blood DNA methylation were assessed in discovery and replication samples (n = ~400 to ~5000) from Generation Scotland.Results
AD genetic risk and two dementia risk scores were associated with differential methylation. The GRS associated predominantly with methylation differences in cis but also identified a genomic region implicated in Parkinson disease. Loci associated with dementia risk scores were enriched for those previously associated with body mass index and alcohol consumption.Discussion
Dementia risk measures show widespread association with blood-based methylation, generating several hypotheses for assessment by future studies.
SUBMITTER: Walker RM
PROVIDER: S-EPMC7416667 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Epigenome-wide analyses identify DNA methylation signatures of dementia risk.
Walker Rosie M RM Bermingham Mairead L ML Vaher Kadi K Morris Stewart W SW Clarke Toni-Kim TK Bretherick Andrew D AD Zeng Yanni Y Amador Carmen C Rawlik Konrad K Pandya Kalyani K Hayward Caroline C Campbell Archie A Porteous David J DJ McIntosh Andrew M AM Marioni Riccardo E RE Evans Kathryn L KL
Alzheimer's & dementia (Amsterdam, Netherlands) 20200810 1
<h4>Introduction</h4>Dementia pathogenesis begins years before clinical symptom onset, necessitating the understanding of premorbid risk mechanisms. Here we investigated potential pathogenic mechanisms by assessing DNA methylation associations with dementia risk factors in Alzheimer's disease (AD)-free participants.<h4>Methods</h4>Associations between dementia risk measures (family history, AD genetic risk score [GRS], and dementia risk scores [combining lifestyle, demographic, and genetic facto ...[more]
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