An epigenome-wide association study of Alzheimer's disease blood highlights robust DNA hypermethylation in the HOXB6 gene
dc.contributor.author | Roubroeks, JAY | |
dc.contributor.author | Smith, AR | |
dc.contributor.author | Smith, RG | |
dc.contributor.author | Pishva, E | |
dc.contributor.author | Ibrahim, Z | |
dc.contributor.author | Sattlecker, M | |
dc.contributor.author | Hannon, EJ | |
dc.contributor.author | Kłoszewska, I | |
dc.contributor.author | Mecocci, P | |
dc.contributor.author | Soininen, H | |
dc.contributor.author | Tsolaki, M | |
dc.contributor.author | Vellas, B | |
dc.contributor.author | Wahlund, LO | |
dc.contributor.author | Aarsland, D | |
dc.contributor.author | Proitsi, P | |
dc.contributor.author | Hodges, A | |
dc.contributor.author | Lovestone, S | |
dc.contributor.author | Newhouse, SJ | |
dc.contributor.author | Dobson, RJB | |
dc.contributor.author | Mill, J | |
dc.contributor.author | van den Hove, DLA | |
dc.contributor.author | Lunnon, K | |
dc.date.accessioned | 2020-09-28T09:51:48Z | |
dc.date.issued | 2020-07-03 | |
dc.description.abstract | A growing number of epigenome-wide association studies have demonstrated a role for DNA methylation in the brain in Alzheimer's disease. With the aim of exploring peripheral biomarker potential, we have examined DNA methylation patterns in whole blood collected from 284 individuals in the AddNeuroMed study, which included 89 nondemented controls, 86 patients with Alzheimer's disease, and 109 individuals with mild cognitive impairment, including 38 individuals who progressed to Alzheimer's disease within 1 year. We identified significant differentially methylated regions, including 12 adjacent hypermethylated probes in the HOXB6 gene in Alzheimer's disease, which we validated using pyrosequencing. Using weighted gene correlation network analysis, we identified comethylated modules of genes that were associated with key variables such as APOE genotype and diagnosis. In summary, this study represents the first large-scale epigenome-wide association study of Alzheimer's disease and mild cognitive impairment using blood. We highlight the differences in various loci and pathways in early disease, suggesting that these patterns relate to cognitive decline at an early stage. | en_GB |
dc.description.sponsorship | Alzheimer's Society, United Kingdom | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | NIH, United States, R01 grant | en_GB |
dc.description.sponsorship | Alzheimer's Research UK | en_GB |
dc.identifier.citation | Vol. 95, pp. 26 - 45 | en_GB |
dc.identifier.doi | 10.1016/j.neurobiolaging.2020.06.023 | |
dc.identifier.grantnumber | AS-PG-14–038 | en_GB |
dc.identifier.grantnumber | MR/N027973/1 | en_GB |
dc.identifier.grantnumber | AG036039 | en_GB |
dc.identifier.grantnumber | ART-EG2010A-2 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/123016 | |
dc.language.iso | en | en_GB |
dc.publisher | Elsevier | en_GB |
dc.rights | © 2020 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) | en_GB |
dc.subject | Alzheimer’s disease (AD) | en_GB |
dc.subject | Biomarker | en_GB |
dc.subject | Blood | en_GB |
dc.subject | DNA methylation | en_GB |
dc.subject | HOXB6 | en_GB |
dc.subject | Mild cognitive impairment (MCI) | en_GB |
dc.title | An epigenome-wide association study of Alzheimer's disease blood highlights robust DNA hypermethylation in the HOXB6 gene | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2020-09-28T09:51:48Z | |
dc.identifier.issn | 0197-4580 | |
dc.description | This is the final version. Available from the publisher via the DOI in this record. | en_GB |
dc.identifier.journal | Neurobiology of Aging | en_GB |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2020-06-27 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2020-07-03 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2020-09-28T09:44:12Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2020-09-28T09:51:52Z | |
refterms.panel | A | en_GB |
refterms.depositException | unlawfulDeposit | |
refterms.depositExceptionExplanation | https://doi.org/10.1016/j.neurobiolaging.2020.06.023 |
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Except where otherwise noted, this item's licence is described as © 2020 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)