A meta-analysis of epigenome-wide association studies in Alzheimer's disease highlights novel differentially methylated loci across cortex.
A meta-analysis of epigenome-wide association studies in Alzheimer's disease highlights novel differentially methylated loci across cortex.
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DOI：
10.1038/s41467-021-23243-4
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发表时间：
2021-06-10
影响因子：
16.6
通讯作者：
Lunnon K
中科院分区：
文献类型：
--
作者：
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
阿尔茨海默病的全表观基因组关联研究强调了神经病理学相关的DNA甲基化差异，尽管现有的研究在样本量上受到限制，并且利用了不同的大脑区域。在这里，我们结合了来自阿尔茨海默病的六项DNA甲基化研究（N = 1453个独特个体）的数据，以确定不同大脑区域和皮层中与Braak阶段相关的甲基化差异。我们在前额叶皮层发现236个CpGs，在颞回发现95个CpGs，在内嗅皮层发现10个CpGs，具有Bonferroni显著性，在小脑中没有。我们的跨皮质荟萃分析（N = 1408名供体）鉴定出220个与神经病理学相关的CpGs，注释到121个基因，其中84个基因之前没有报道过这种显著性阈值。我们使用另外两个DNA甲基组数据集复制了我们的发现，这些数据集由另外600个独特的捐赠者组成。荟萃分析汇总统计数据可在我们的在线数据资源（www.epigenomicslab.com/ad-meta-analysis/）中获得。尽管阿尔茨海默病的全表观基因组关联研究强调了神经病理学相关的DNA甲基化差异，但先前的研究在样本量和使用的脑区域方面受到限制。在这里，作者结合了来自阿尔茨海默病的六项DNA甲基化研究的数据（N = 1453个独特的个体），以确定皮层中甲基化的差异位点。
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/). Although epigenome-wide association studies of Alzheimer’s disease have highlighted neuropathology-associated DNA methylation differences, previous studies have been limited in sample size and brain region used. Here, the authors combine data from six DNA methylomic studies of Alzheimer’s disease (N = 1453 unique individuals) to identify differentially methylated loci across cortex.
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影响因子：
25
作者：
Lunnon, Katie;Smith, Rebecca;Hannon, Eilis;De Jager, Philip L.;Srivastava, Gyan;Volta, Manuela;Troakes, Claire;Al-Sarraj, Safa;Burrage, Joe;Macdonald, Ruby;Condliffe, Daniel;Harries, Lorna W.;Katsel, Pavel;Haroutunian, Vahram;Kaminsky, Zachary;Joachim, Catharine;Powell, John;Lovestone, Simon;Bennett, David A.;Schalkwyk, Leonard C.;Mill, Jonathan
通讯作者：
Mill, Jonathan
DOI：
10.1016/s0140-6736(20)32205-4
发表时间：
2021-04-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Scheltens P;De Strooper B;Kivipelto M;Holstege H;Chételat G;Teunissen CE;Cummings J;van der Flier WM
通讯作者：
van der Flier WM
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
5.8
作者：
Chakraborty, Sutirtha;Datta, Somnath;Datta, Susmita
通讯作者：
Datta, Susmita
XQTL图整合了人脑的转录组和表观基因组的遗传结构。
影响因子：
25
作者：
Ng B;White CC;Klein HU;Sieberts SK;McCabe C;Patrick E;Xu J;Yu L;Gaiteri C;Bennett DA;Mostafavi S;De Jager PL
通讯作者：
De Jager PL