Alzheimer's research & therapy · 2023
Entorhinal cortex epigenome-wide association study highlights four novel loci showing differential methylation in Alzheimer's disease.
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Sommerer Yasmine, Dobricic Valerija, Schilling Marcel, Ohlei Olena, Sabet Sanaz Sedghpour, Wesse Tanja, Fuß Janina, Franzenburg Sören, Franke Andre, Parkkinen Laura, Lill Christina M, Bertram Lars
Аннотация
BACKGROUND: Studies on DNA methylation (DNAm) in Alzheimer's disease (AD) have recently highlighted several genomic loci showing association with disease onset and progression.
METHODS: Here, we conducted an epigenome-wide association study (EWAS) using DNAm profiles in entorhinal cortex (EC) from 149 AD patients and control brains and combined these with two previously published EC datasets by meta-analysis (total n = 337).
RESULTS: We identified 12 cytosine-phosphate-guanine (CpG) sites showing epigenome-wide significant association with either case-control status or Braak's tau-staging. Four of these CpGs, located in proximity to CNFN/LIPE, TENT5A, PALD1/PRF1, and DIRAS1, represent novel findings. Integrating DNAm levels with RNA sequencing-based mRNA expression data generated in the same individuals showed significant DNAm-mRNA correlations for 6 of the 12 significant CpGs. Lastly, by calculating rates of epigenetic age acceleration using two recently proposed "epigenetic clock" estimators we found a significant association with accelerated epigenetic aging in the brains of AD patients vs. controls.
CONCLUSION: In summary, our study represents the hitherto most comprehensive EWAS in AD using EC and highlights several novel differentially methylated loci with potential effects on gene expression.
METHODS: Here, we conducted an epigenome-wide association study (EWAS) using DNAm profiles in entorhinal cortex (EC) from 149 AD patients and control brains and combined these with two previously published EC datasets by meta-analysis (total n = 337).
RESULTS: We identified 12 cytosine-phosphate-guanine (CpG) sites showing epigenome-wide significant association with either case-control status or Braak's tau-staging. Four of these CpGs, located in proximity to CNFN/LIPE, TENT5A, PALD1/PRF1, and DIRAS1, represent novel findings. Integrating DNAm levels with RNA sequencing-based mRNA expression data generated in the same individuals showed significant DNAm-mRNA correlations for 6 of the 12 significant CpGs. Lastly, by calculating rates of epigenetic age acceleration using two recently proposed "epigenetic clock" estimators we found a significant association with accelerated epigenetic aging in the brains of AD patients vs. controls.
CONCLUSION: In summary, our study represents the hitherto most comprehensive EWAS in AD using EC and highlights several novel differentially methylated loci with potential effects on gene expression.