An epigenome-wide association study of Alzheimer's disease blood highlights robust DNA hypermethylation in the HOXB6 gene.
An epigenome-wide association study of Alzheimer's disease blood highlights robust DNA hypermethylation in the HOXB6 gene.
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DOI：
10.1016/j.neurobiolaging.2020.06.023
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发表时间：
2020-11
影响因子：
4.2
通讯作者：
Lunnon K
中科院分区：
文献类型：
--
作者：
Roubroeks JAY;Smith AR;Smith RG;Pishva E;Ibrahim Z;Sattlecker M;Hannon EJ;Kłoszewska I;Mecocci P;Soininen H;Tsolaki M;Vellas B;Wahlund LO;Aarsland D;Proitsi P;Hodges A;Lovestone S;Newhouse SJ;Dobson RJB;Mill J;van den Hove DLA;Lunnon K
越来越多的表观基因组关联研究已经证明了DNA甲基化在阿尔茨海默病中的作用。为了探索外周生物标志物的潜力，我们检查了从AddNeuroMed研究中收集的284名个体的全血中的DNA甲基化模式，其中包括89名非痴呆对照，86名阿尔茨海默病患者和109名轻度认知障碍患者，包括38名在1年内进展为阿尔茨海默病的个体。我们确定了显着的差异甲基化区域，包括12个相邻的超甲基化探针在阿尔茨海默病的HOXB 6基因，我们验证了焦磷酸测序。使用加权基因相关网络分析，我们确定了与APOE基因型和诊断等关键变量相关的基因的共甲基化模块。总之，这项研究代表了第一个使用血液进行的阿尔茨海默病和轻度认知障碍的大规模表观基因组关联研究。我们强调了早期疾病中各种位点和途径的差异，这表明这些模式与早期阶段的认知能力下降有关。我们对阿尔茨海默病、轻度认知障碍和对照全血中的DNA甲基化进行了表观基因组范围的评估。我们观察到HOXB 6在AD中的高甲基化，这是通过焦磷酸测序验证的。网络分析（加权基因相关网络分析）显示疾病中免疫系统通路的差异。
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. We performed an epigenome-wide assessment of DNA methylation in Alzheimer's disease, mild cognitive impairment, and control whole blood. We observed hypermethylation of HOXB6 in AD, which was validated via pyrosequencing. Network analysis (weighted gene correlation network analysis) showed differences in immune system pathways in disease.
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影响因子：
14
作者：
通讯作者：
--
影响因子：
14.5
作者：
Hye, A.;Lynham, S.;Lovestone, S.
通讯作者：
Lovestone, S.
差异基因表达谱取决于外周血收集和RNA分离的方法。
影响因子：
4.4
作者：
Asare, Adam L.;Kolchinsky, Svetlana A.;Gao, Zhong;Wang, Richard;Raddassi, Khadir;Bourcier, Katarzyna;Seyfert-Margolis, Vicki
通讯作者：
Seyfert-Margolis, Vicki
影响因子：
4
作者：
Furney, Simon J.;Kronenberg, Deborah;Lovestone, Simon
通讯作者：
Lovestone, Simon
影响因子：
25
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.
通讯作者：
Bennett, David A.