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

ORCID
0000-0003-2323-9340
Affiliation
Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany
Sommerer, Yasmine;
Affiliation
Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany
Dobricic, Valerija;
ORCID
0000-0002-3453-7792
Affiliation
Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany
Schilling, Marcel;
Affiliation
Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany
Ohlei, Olena;
Affiliation
Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Campus Clínic August Pi i Sunyer, Casanova, 143, 08036 Barcelona, Spain
Bartrés-Faz, David;
Affiliation
Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Garcilaso, 57, 08027 Barcelona, Spain
Cattaneo, Gabriele;
Affiliation
Biology of Aging Working Group, Department of Endocrinology and Metabolic Diseases, Division of Lipid Metabolism, Charité—Universitätsmedizin Berlin (corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin), Augustenburger Platz 1, 13353 Berlin, Germany
Demuth, Ilja;
Affiliation
Center for Lifespan Psychology, Max Planck Institute for Human Development, Lentzeallee 94, 14195 Berlin, Germany
Düzel, Sandra;
Affiliation
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Christian-Albrechts-Platz 4, 24118 Kiel, Germany
Franzenburg, Sören;
ORCID
0000-0002-7631-9355
Affiliation
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Christian-Albrechts-Platz 4, 24118 Kiel, Germany
Fuß, Janina;
Affiliation
Center for Lifespan Psychology, Max Planck Institute for Human Development, Lentzeallee 94, 14195 Berlin, Germany
Lindenberger, Ulman;
ORCID
0000-0001-8975-0382
Affiliation
Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Garcilaso, 57, 08027 Barcelona, Spain
Pascual-Leone, Álvaro;
Affiliation
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Christian-Albrechts-Platz 4, 24118 Kiel, Germany
Sabet, Sanaz Sedghpour;
Affiliation
Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Campus Clínic August Pi i Sunyer, Casanova, 143, 08036 Barcelona, Spain
Solé-Padullés, Cristina;
Affiliation
Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Garcilaso, 57, 08027 Barcelona, Spain
Tormos, Josep M.;
ORCID
0000-0001-5003-7766
Affiliation
Biology of Aging Working Group, Department of Endocrinology and Metabolic Diseases, Division of Lipid Metabolism, Charité—Universitätsmedizin Berlin (corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin), Augustenburger Platz 1, 13353 Berlin, Germany
Vetter, Valentin Max;
Affiliation
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Christian-Albrechts-Platz 4, 24118 Kiel, Germany
Wesse, Tanja;
Affiliation
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Christian-Albrechts-Platz 4, 24118 Kiel, Germany
Franke, Andre;
Affiliation
Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany
Lill, Christina M.;
ORCID
0000-0002-0108-124X
Affiliation
Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany
Bertram, Lars

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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