36c6aa6ce33796967b41e323fe91e97c pmc_9687249.pdf f2c85ce9e559515547dec1c33b91ed910ff6f481 pmc_9687249.pdf ed8d01895b21002770cd861d35110639bdf5e9d8d7383e1088b229260ba6c663 pmc_9687249.pdf Title: Epigenome-Wide Association Study in Peripheral Tissues Highlights DNA Methylation Profiles Associated with Episodic Memory Performance in Humans Subject: 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. Keywords: DNA methylation; CpG; epigenome-wide association study; EWAS; episodic memory; cross-sectional; longitudinal Author: Yasmine Sommerer, Valerija Dobricic, Marcel Schilling, Olena Ohlei, David Bartrés-Faz, Gabriele Cattaneo, Ilja Demuth, Sandra Düzel, Sören Franzenburg, Janina Fuß, Ulman Lindenberger, Álvaro Pascual-Leone, Sanaz Sedghpour Sabet, Cristina Solé-Padullés, Josep M. Tormos, Valentin Max Vetter, Tanja Wesse, Andre Franke, Christina M. Lill and Lars Bertram Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Nov 10 08:34:27 2022 CET ModDate: Thu Nov 10 08:45:07 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1649854 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BBAXXJ+VnURWPalladioL Type 1 Custom yes yes no 10 0 LJUMOE+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 ONGYHW+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 DVSNEJ+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 QMDDXF+CMSY10 Type 1 Builtin yes yes no 28 0 AIPYBR+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 EBFBTV+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 50 0 ZPAZMK+URWPalladioL-BoldItal Type 1 Custom yes yes no 75 0 RHQYUV+CMBSY10 Type 1 Builtin yes yes no 79 0 FCRHJY+EURM10 Type 1 Builtin yes yes no 86 0 XATTIN+PazoMath-Italic Type 1 Builtin yes yes no 108 0 SYVAVM+VnURWPalladioL-Italic Type 1 Custom yes yes no 128 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-09-08 02:40:57 CEST RepresentationInformation: pmc_9687249.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-08-04 02:19:36 CEST Size: 1649854 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 397 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Human Samples and Measurements of Episodic Memory Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Episodic Memory Phenotypes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: DNA Extraction and Processing Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: DNA Methylation Profiling Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: DNA Methylation Data Processing and Quality Control Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Epigenome-Wide Association Analyses to Identify Differentially Methylated Probes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Calculation of Poly-Epigenetic Scores (PESs) for General Cognitive Abilities and AD Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Epigenetic Age Estimation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Look-Up of EM-Associated CpGs in an Independent EWAS on AD-Related Phenotypes in Human EC Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Look-Up of EM-Associated CpGs in an Independent Buccal Brain Correlation Map Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Look-Up of EM-Associated CpGs in a Buccal mQTL Database Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: DNAm mRNA Correlation Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Children: Item: Title: EM Performance Measures in the Analyzed Datasets Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: EWAS Meta-Analyses Highlight Several CpG Loci Showing at Least Genome-Wide Suggestive Association with Cross-Sectional and Longitudinal Changes in EM Performance Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Poly-Epigenetic Score Analysis for Cognitive Abilities and AD Show Only Little Correspondence with Episodic Memory EWAS Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Correspondence of EWAS Results in Blood and Buccal Samples Underscores Tissue Specificity Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Correlation Analysis between DNAm Levels and mRNA Expression in Human Brain Samples Highlights Three Loci Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Horvath Epigenetic Age Acceleration Is Not Associated with EM Performance Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Info: Title: Epigenome-Wide Association Study in Peripheral Tissues Highlights DNA Methylation Profiles Associated with Episodic Memory Performance in Humans Author: Yasmine Sommerer, Valerija Dobricic, Marcel Schilling, Olena Ohlei, David Bartrés-Faz, Gabriele Cattaneo, Ilja Demuth, Sandra Düzel, Sören Franzenburg, Janina Fuß, Ulman Lindenberger, Álvaro Pascual-Leone, Sanaz Sedghpour Sabet, Cristina Solé-Padullés, Josep M. Tormos, Valentin Max Vetter, Tanja Wesse, Andre Franke, Christina M. Lill and Lars Bertram Subject: 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. 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