Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci.
Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci.
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DOI：
10.1038/nn.3786
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发表时间：
2014-09
影响因子：
25
通讯作者：
Bennett, David A.
中科院分区：
文献类型：
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作者：
De Jager, Philip L.;Srivastava, Gyan;Lunnon, Katie;Burgess, Jeremy;Schalkwyk, Leonard C.;Yu, Lei;Eaton, Matthew L.;Keenan, Brendan T.;Ernst, Jason;McCabe, Cristin;Tang, Anna;Raj, Towfique;Replogle, Joseph;Brodeur, Wendy;Gabriel, Stacey;Chai, High S.;Younkin, Curtis;Younkin, Steven G.;Zou, Fanggeng;Szyf, Moshe;Epstein, Charles B.;Schneider, Julie A.;Bernstein, Bradley E.;Meissner, Alex;Ertekin-Taner, Nilufer;Chibnik, Lori B.;Kellis, Manolis;Mill, Jonathan;Bennett, David A.
在这里，我们利用708个前瞻性收集的尸检大脑的独特集合来评估与阿尔茨海默病（AD）相关的大脑DNA的甲基化状态。我们发现，在415，848个询问的CpG中，有71个的甲基化水平与AD病理学的负担显著相关，包括ABCA7和BIN1区域的CpG，这些区域含有已知的AD易感性变体。我们验证了11个差异甲基化的区域在一个独立的117名受试者。此外，我们在功能上验证了这些CpG关联，并鉴定了AD中RNA表达改变的附近基因：ANK1，CDH23，DIP2A，RHBDF2，RPL13，RNF34，SERPINF1和SERPINF2。我们的分析表明，这些DNA甲基化变化可能在AD的发病中起作用，因为（1）它们在症状前受试者中观察到，（2）六个经验证的基因与已知的AD易感基因网络连接。
Here, we leverage a unique 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 find that the level of methylation at 71 of the 415,848 interrogated CpGs is significantly associated with the burden of AD pathology, including CpGs in the ABCA7 and BIN1 regions, which harbor known AD susceptibility variants. We validate 11 of the differentially methylated regions in an independent set of 117 subjects. Further, we functionally validate these CpG associations and identify the nearby genes whose RNA expression is altered in AD: ANK1, CDH23, DIP2A, RHBDF2, RPL13, RNF34, SERPINF1 and SERPINF2. Our analyses suggest that these DNA methylation changes may have a role in the onset of AD since (1) they are seen in presymptomatic subjects and (2) six of the validated genes connect to a known AD susceptibility gene network.
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影响因子：
11.2
作者：
Chibnik, Lori B.;Shulman, Joshua M.;Leurgans, Sue E.;Schneider, Julie A.;Wilson, Robert S.;Tran, Dong;Aubin, Cristin;Buchman, Aron S.;Heward, Christopher B.;Myers, Amanda J.;Hardy, John A.;Huentelman, Matthew J.;Corneveaux, Jason J.;Reiman, Eric M.;Evans, Denis A.;Bennett, David A.;De Jager, Philip L.
通讯作者：
De Jager, Philip L.
影响因子：
11.2
作者：
Bennett, David A.;Wilson, Robert S.;Boyle, Patricia A.;Buchman, Aron S.;Schneider, Julie A.
通讯作者：
Schneider, Julie A.
影响因子：
29
作者：
Akbarian, Schahram;Beeri, Michal Schnaider;Haroutunian, Vahram
通讯作者：
Haroutunian, Vahram
DOI：
10.1073/pnas.1302553110
发表时间：
2013-07-09
影响因子：
11.1
作者：
Maretzky, Thorsten;McIlwain, David R.;Blobel, Carl P.
通讯作者：
Blobel, Carl P.
影响因子：
46.9
作者：
通讯作者：
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