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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021, The Author(s).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/).
Author(s): Smith RG, Pishva E, Shireby G, Smith AR, Roubroeks JAY, Hannon E, Wheildon G, Mastroeni D, Gasparoni G, Riemenschneider M, Giese A, Sharp AJ, Schalkwyk L, Haroutunian V, Viechtbauer W, van den Hove DLA, Weedon M, Brokaw D, Francis PT, Thomas AJ, Love S, Morgan K, Walter J, Coleman PD, Bennett DA, De Jager PL, Mill J, Lunnon K
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2021
Volume: 12
Issue: 1
Online publication date: 10/06/2021
Acceptance date: 16/04/2021
Date deposited: 21/06/2021
ISSN (electronic): 2041-1723
Publisher: Nature Research
URL: https://doi.org/10.1038/s41467-021-23243-4
DOI: 10.1038/s41467-021-23243-4
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