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dc.contributor.authorDe Jager, PL
dc.contributor.authorSrivastava, G.P.
dc.contributor.authorLunnon, Katie
dc.contributor.authorBurgess, J
dc.contributor.authorSchalkwyk, Leonard
dc.contributor.authorYu, L
dc.contributor.authorEaton, ML
dc.contributor.authorKeenan, BT
dc.contributor.authorErnst, J
dc.contributor.authorMcCabe, C
dc.contributor.authorTang, A
dc.contributor.authorRaj, T
dc.contributor.authorReplogle, J
dc.contributor.authorBrodeur, W
dc.contributor.authorGabriel, S
dc.contributor.authorChai, HS
dc.contributor.authorYounkin, C
dc.contributor.authorYounkin, SG
dc.contributor.authorZou, F
dc.contributor.authorSzyf, M
dc.contributor.authorEpstein, CB
dc.contributor.authorSchneider, J.
dc.contributor.authorBernstein, BE
dc.contributor.authorMeissner, A
dc.contributor.authorErtekin-Taner, N
dc.contributor.authorChibnik, LB
dc.contributor.authorKellis, M
dc.contributor.authorMill, J
dc.contributor.authorBennett, DA
dc.date.accessioned2016-02-11T11:40:50Z
dc.date.issued2014-08-17
dc.description.abstractWe used a collection of 708 prospectively collected autopsied brains to assess the methylation state of the brain's DNA in relation to Alzheimer's disease (AD). We found that the level of methylation at 71 of the 415,848 interrogated CpGs was significantly associated with the burden of AD pathology, including CpGs in the ABCA7 and BIN1 regions, which harbor known AD susceptibility variants. We validated 11 of the differentially methylated regions in an independent set of 117 subjects. Furthermore, we functionally validated these CpG associations and identified the nearby genes whose RNA expression was altered in AD: ANK1, CDH23, DIP2A, RHBDF2, RPL13, SERPINF1 and SERPINF2. Our analyses suggest that these DNA methylation changes may have a role in the onset of AD given that we observed them in presymptomatic subjects and that six of the validated genes connect to a known AD susceptibility gene network.en_GB
dc.description.sponsorshipNational Institute of Healthen_GB
dc.description.sponsorshipSiragusa Foundationen_GB
dc.description.sponsorshipRobert and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Programen_GB
dc.description.sponsorshipAlzheimer's Research UKen_GB
dc.identifier.citationVol. 17 (9), pp. 1156 - 1163en_GB
dc.identifier.doi10.1038/nn.3786
dc.identifier.grantnumberR01 AG036042en_GB
dc.identifier.grantnumberR01AG036836en_GB
dc.identifier.grantnumberR01 AG17917en_GB
dc.identifier.grantnumberR01AG15819en_GB
dc.identifier.grantnumberR01 AG032990en_GB
dc.identifier.grantnumberR01 AG18023en_GB
dc.identifier.grantnumberRC2 AG036547en_GB
dc.identifier.grantnumberP30 AG10161en_GB
dc.identifier.grantnumberP50 AG016574en_GB
dc.identifier.grantnumberU01 ES017155en_GB
dc.identifier.grantnumberKL2 RR024151en_GB
dc.identifier.grantnumberK25 AG041906-01en_GB
dc.identifier.grantnumberAG036039en_GB
dc.identifier.urihttp://hdl.handle.net/10871/19711
dc.language.isoenen_GB
dc.publisherNature Publishing Groupen_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/25129075en_GB
dc.rights© 2014 Nature America, Inc. All rights reserved.en_GB
dc.subjectAdaptor Proteins, Signal Transducingen_GB
dc.subjectAgeden_GB
dc.subjectAged, 80 and overen_GB
dc.subjectAlzheimer Diseaseen_GB
dc.subjectAmyloidosisen_GB
dc.subjectAnkyrinsen_GB
dc.subjectBrainen_GB
dc.subjectCarrier Proteinsen_GB
dc.subjectCpG Islandsen_GB
dc.subjectDNA Methylationen_GB
dc.subjectFemaleen_GB
dc.subjectGenetic Predisposition to Diseaseen_GB
dc.subjectGenome-Wide Association Studyen_GB
dc.subjectHumansen_GB
dc.subjectMaleen_GB
dc.subjectMiddle Ageden_GB
dc.subjectNuclear Proteinsen_GB
dc.subjectProtein Interaction Mapsen_GB
dc.subjectTumor Suppressor Proteinsen_GB
dc.titleAlzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other locien_GB
dc.typeArticleen_GB
dc.date.available2016-02-11T11:40:50Z
dc.identifier.issn1097-6256
exeter.place-of-publicationUnited States
dc.identifier.journalNature Neuroscienceen_GB


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