TY - JOUR
T1 - Epigenome-Wide Association Study in Peripheral Tissues Highlights DNA Methylation Profiles Associated with Episodic Memory Performance in Humans
AU - Sommerer, Yasmine
AU - Dobricic, Valerija
AU - Schilling, Marcel
AU - Ohlei, Olena
AU - Bartrés-Faz, David
AU - Cattaneo, Gabriele
AU - Demuth, Ilja
AU - Düzel, Sandra
AU - Franzenburg, Sören
AU - Fuß, Janina
AU - Lindenberger, Ulman
AU - Pascual-Leone, Álvaro
AU - Sabet, Sanaz Sedghpour
AU - Solé-Padullés, Cristina
AU - Tormos, Josep M.
AU - Vetter, Valentin Max
AU - Wesse, Tanja
AU - Franke, Andre
AU - Lill, Christina M.
AU - Bertram, Lars
N1 - Funding Information:
This work was supported by the EU Horizon 2020 Fund (as part of the “Lifebrain” consortium, #732592) to LB, by the Cure Alzheimer’s Fund (as part of the “CIRCUITS” consortium) to LB, and by Deutsche Forschungsgemeinschaft (DFG) and the National Science Foundation China (NSFC) as part of the Joint Sino-German research project (“MiRNet-AD”, #391523883) to LB. The BASE-II research project (Co-PIs: Lars Bertram, Ilja Demuth, Denis Gerstorf, Ulman Lindenberger, Graham Pawelec, Elisabeth Steinhagen-Thiessen, and Gert G. Wagner) was supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) under grant numbers #16SV5536K, #16SV5537, #16SV5538, #16SV5837, #01UW0808, 01GL1716A, and 01GL1716B. BBHI has received funding from the “la Caixa” Foundation (grant agreement n° LCF/PR/PR16/11110004), Institut Guttmann and Fundació Abertis. D.B.F. is partially supported by an ICREA Academia 2019 award and a Spanish Ministry of Science, Innovation and Universities (MICIU/FEDER; RTI2018-095181-B-C21) grant. CML is supported by the Heisenberg Program of the DFG (LI 2654/4-1).
Funding Information:
The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this manuscript were obtained from the GTEx Portal, accessed on 25 August 2021. We acknowledge the high-performance environment (“OmicsCluster”) at the University of Lübeck where most data processing and analysis steps of this study were run.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85141830860&partnerID=8YFLogxK
U2 - 10.3390/biomedicines10112798
DO - 10.3390/biomedicines10112798
M3 - Journal articles
AN - SCOPUS:85141830860
SN - 2227-9059
VL - 10
JO - Biomedicines
JF - Biomedicines
IS - 11
M1 - 2798
ER -
