Abstract / Description of output

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.
Original languageEnglish
Article numbere12078
JournalAlzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Volume12
Issue number1
Early online date10 Aug 2020
DOIs
Publication statusPublished - 10 Aug 2020

Fingerprint

Dive into the research topics of 'Epigenome-wide analyses identify DNA methylation signatures of dementia risk'. Together they form a unique fingerprint.

Cite this