Whole genome methylation sequencing in blood identifies extensive differential DNA methylation in late-onset dementia due to Alzheimer's disease.
Whole genome methylation sequencing in blood identifies extensive differential DNA methylation in late-onset dementia due to Alzheimer's disease.
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血液中的全基因组甲基化测序发现了阿尔茨海默病引起的迟发性痴呆症中广泛的差异 DNA 甲基化。
DOI：
10.1002/alz.13514
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Hogan,KirkJ
中科院分区：
文献类型：
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作者：
Breen,Coleman;Papale,LigiaA;Clark,LindsayR;Bergmann,PhillipE;Madrid,Andy;Asthana,Sanjay;Johnson,SterlingC;Keleş,Sündüz;Alisch,ReidS;Hogan,KirkJ
引言基于DNA微阵列的研究报告了阿尔茨海默病（AD）所致迟发性痴呆和认知未受损个体之间血液中的差异甲基化位置（DMPs），但询问< 4%的基因组。来自108名AD和173名认知未受损个体的281份血液样品中的826个CpG基因座dPTSWGMS在整个人类甲基化组中鉴定了28，038个DMP，包括2707个差异甲基化基因（例如，SORCS 3、GABA和PICALM）编码与AD相关的生物学途径中的蛋白质，如突触膜、阳离子通道复合物，173个差异甲基化的血液特异性增强子与95个基因的启动子相互作用，这些基因在患有和没有AD的人的血液中差异表达。有和没有AD的人。亮点全基因组DNA甲基化水平在有和没有阿尔茨海默病（AD）的人的血液中进行定量。鉴定了2838个差异甲基化位置（DMP）。2707个基因组成DMP。75个独立的AD遗传风险位点中有48个具有DMP。1568个血液特异性增强子组成DMP，其中173个与95个基因的启动子相互作用，这些基因在患有和没有AD的人的血液中差异表达。
INTRODUCTIONDNA microarray‐based studies report differentially methylated positions (DMPs) in blood between late‐onset dementia due to Alzheimer's disease (AD) and cognitively unimpaired individuals, but interrogate < 4% of the genome.METHODSWe used whole genome methylation sequencing (WGMS) to quantify DNA methylation levels at 25,409,826 CpG loci in 281 blood samples from 108 AD and 173 cognitively unimpaired individuals.RESULTSWGMS identified 28,038 DMPs throughout the human methylome, including 2707 differentially methylated genes (e.g.,SORCS3,GABA, andPICALM) encoding proteins in biological pathways relevant to AD such as synaptic membrane, cation channel complex, and glutamatergic synapse. One hundred seventy‐three differentially methylated blood‐specific enhancers interact with the promoters of 95 genes that are differentially expressed in blood from persons with and without AD.DISCUSSIONWGMS identifies differentially methylated CpGs in known and newly detected genes and enhancers in blood from persons with and without AD.HighlightsWhole genome DNA methylation levels were quantified in blood from persons with and without Alzheimer's disease (AD).Twenty‐eight thousand thirty‐eight differentially methylated positions (DMPs) were identified.Two thousand seven hundred seven genes comprise DMPs.Forty‐eight of 75 independent genetic risk loci for AD have DMPs.One thousand five hundred sixty‐eight blood‐specific enhancers comprise DMPs, 173 of which interact with the promoters of 95 genes that are differentially expressed in blood from persons with and without AD.