TY - JOUR
T1 - Entorhinal cortex epigenome-wide association study highlights four novel loci showing differential methylation in Alzheimer’s disease
AU - Sommerer, Yasmine
AU - Dobricic, Valerija
AU - Schilling, Marcel
AU - Ohlei, Olena
AU - Sabet, Sanaz Sedghpour
AU - Wesse, Tanja
AU - Fuß, Janina
AU - Franzenburg, Sören
AU - Franke, Andre
AU - Parkkinen, Laura
AU - Lill, Christina M.
AU - Bertram, Lars
N1 - Funding Information:
Open Access funding enabled and organized by Projekt DEAL. This work was supported by the Cure Alzheimer’s Fund (as part of the “CIRCUITS” consortium) to L.B., the EU Horizon 2020 Fund (as part of the “Lifebrain” consortium, #732592) to L.B., and by the Deutsche Forschungsgemeinschaft (DFG) and the National Science Foundation China (NSFC) as part of the Joint Sino-German research project (“MiRNet-AD”, #391523883) to L.B. Additional support was provided by the DFG Research Infrastructure NGS_CC (project 407495230) as part of the Next Generation Sequencing Competence Network (#423957469). NGS analyses were carried out at the Competence Centre for Genomic Analysis (Kiel). The Oxford Brain Bank is supported by the Brains for Dementia Research (BDR) (Alzheimer Society and Alzheimer Research UK) and the NIHR Oxford Biomedical Research Centre. C.M.L. is supported CML by the Heisenberg Program of the DFG (LI 2654/4–1).
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/5/6
Y1 - 2023/5/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85157997291&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/ef6726d9-e0f2-3b08-a236-ee7362c70fab/
U2 - 10.1186/s13195-023-01232-7
DO - 10.1186/s13195-023-01232-7
M3 - Journal articles
C2 - 37149695
AN - SCOPUS:85157997291
SN - 1758-9193
VL - 15
SP - 92
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
IS - 1
M1 - 92
ER -
