Epigenome-Wide Association Study in Peripheral Tissues Highlights DNA Methylation Profiles Associated with Episodic Memory Performance in Humans

Abstract

The decline in episodic memory (EM) performance is a hallmark of cognitive aging and an early clinical sign in Alzheimer’s disease (AD). In this study, we conducted an epigenome-wide association study (EWAS) using DNA methylation (DNAm) profiles from buccal and blood samples for cross-sectional (n = 1019) and longitudinal changes in EM performance (n = 626; average follow-up time 5.4 years) collected under the auspices of the Lifebrain consortium project. The mean age of participants with cross-sectional data was 69 ± 11 years (30–90 years), with 50% being females. We identified 21 loci showing suggestive evidence of association (p < 1 × 10−5) with either or both EM phenotypes. Among these were SNCA, SEPW1 (both cross-sectional EM), ITPK1 (longitudinal EM), and APBA2 (both EM traits), which have been linked to AD or Parkinson’s disease (PD) in previous work. While the EM phenotypes were nominally significantly (p < 0.05) associated with poly-epigenetic scores (PESs) using EWASs on general cognitive function, none remained significant after correction for multiple testing. Likewise, estimating the degree of “epigenetic age acceleration” did not reveal significant associations with either of the two tested EM phenotypes. In summary, our study highlights several interesting candidate loci in which differential DNAm patterns in peripheral tissue are associated with EM performance in humans.

Current evidence supporting associations of DNA methylation measurements with survivorship burdens in cancer survivors: A scoping review

“…There is a growing body of evidence that supports associations of DNAm patterns and health outcomes related to survivorship. Associations of epigenetics and cognitive function have been identified in the elderly and in disease states such as dementia or Alzheimer's 78–80 . More examples include identified DNAm associations with of depression, fatigue, pain, and cardiovascular comorbidities 81–85 .…”

“…There is a growing body of evidence that supports associations of DNAm patterns and health outcomes related to Associations of epigenetics and cognitive function have been identified in the elderly and in disease states such as dementia or Alzheimer's. [78][79][80] More examples include identified DNAm associations with of depression, fatigue, pain, and cardiovascular comorbidities. [81][82][83][84][85] Given the known associations of DNAm with various clinical outcomes already, steps with respect to patient sample selection can be taken in DNAm studies to ensure observed differences are specific to cancer survivorship.…”

Genome-wide QTL mapping across three tissues highlights several Alzheimer’s and Parkinson’s disease loci potentially acting via DNA methylation

“…DNA for all samples was extracted using standard procedures as described previously (BASE-II & BBHI: ref. 14 ;LCBC: ref. 38).…”

“…DNAm was measured using the Infinium Human MethylationEPIC array (Illumina, Inc., USA) at the Institute of Clinical Molecular Biology at UKSH Campus Kiel on an iScan instrument according to the manufacturer's recommendations. QC and data processing were performed using the same procedures as described previously 12,14 . Briefly, data pre-processing was performed in R (version 3.6.1) using the package bigmelon (version 1.22.0) with default settings 45 .…”

“…One method to probe for epigenetic effects on disease risk is to conduct epigenome-wide association studies (EWAS). In AD, several such EWAS have been published using both brain [9][10][11][12][13] and peripheral tissues [14][15][16] highlighting a number of CpG sites that show differential DNAm with respect to disease state. Similar EWAS efforts have been completed in PD, e.g.…”