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A meta-analysis of epigenome-wide association studies in Alzheimer's disease highlights novel differentially methylated loci across cortex.

Smith, Rebecca G and Pishva, Ehsan and Shireby, Gemma and Smith, Adam R and Roubroeks, Janou AY and Hannon, Eilis and Wheildon, Gregory and Mastroeni, Diego and Gasparoni, Gilles and Riemenschneider, Matthias and Giese, Armin and Sharp, Andrew J and Schalkwyk, Leonard and Haroutunian, Vahram and Viechtbauer, Wolfgang and van den Hove, Daniel LA and Weedon, Michael and Brokaw, Danielle and Francis, Paul T and Thomas, Alan J and Love, Seth and Morgan, Kevin and Walter, Jörn and Coleman, Paul D and Bennett, David A and De Jager, Philip L and Mill, Jonathan and Lunnon, Katie (2021) 'A meta-analysis of epigenome-wide association studies in Alzheimer's disease highlights novel differentially methylated loci across cortex.' Nature Communications, 12 (1). ISSN 2041-1723

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Abstract

Epigenome-wide association studies of Alzheimer's disease have highlighted neuropathology-associated DNA methylation differences, although existing studies have been limited in sample size and utilized different brain regions. Here, we combine data from six DNA methylomic studies of Alzheimer's disease (N = 1453 unique individuals) to identify differential methylation associated with Braak stage in different brain regions and across cortex. We identify 236 CpGs in the prefrontal cortex, 95 CpGs in the temporal gyrus and ten CpGs in the entorhinal cortex at Bonferroni significance, with none in the cerebellum. Our cross-cortex meta-analysis (N = 1408 donors) identifies 220 CpGs associated with neuropathology, annotated to 121 genes, of which 84 genes have not been previously reported at this significance threshold. We have replicated our findings using two further DNA methylomic datasets consisting of a further >600 unique donors. The meta-analysis summary statistics are available in our online data resource ( www.epigenomicslab.com/ad-meta-analysis/ ).

Item Type: Article
Uncontrolled Keywords: Entorhinal Cortex, Prefrontal Cortex, Temporal Lobe, Humans, Alzheimer Disease, Cohort Studies, ROC Curve, DNA Methylation, Epigenesis, Genetic, CpG Islands, Aged, Aged, 80 and over, Middle Aged, Female, Male, Genome-Wide Association Study, Epigenome
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Elements
Date Deposited: 03 Sep 2021 11:41
Last Modified: 03 Sep 2021 11:41
URI: http://repository.essex.ac.uk/id/eprint/31044

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