神经病理学
DNA甲基化
生物
表观遗传学
遗传学
表观基因组
甲基化
亚硫酸氢盐测序
基因
病理
疾病
基因表达
医学
作者
Helena Palma‐Gudiel,Lei Yu,Zhiguang Huo,Jingyun Yang,Yanling Wang,Tongjun Gu,Cheng Gao,Philip L. De Jager,Peng Jin,David A. Bennett,Jinying Zhao
摘要
Abstract Introduction Our previous epigenome‐wide association study (EWAS) of Alzheimer's disease (AD) in human brain identified 71 CpGs associated with AD pathology. However, due to low coverage of the Illumina platform, many important CpGs might have been missed. Methods In a large collection of human brain tissue samples ( N = 864), we fine‐mapped previous EWAS loci by targeted bisulfite sequencing and examined their associations with AD neuropathology. DNA methylation was also linked to gene expression of the same brain cortex. Results Our targeted sequencing captured 130 CpGs (∼1.2 kb), 93 of which are novel. Of the 130 CpGs, 57 sites (only 17 included in previous EWAS) and 12 gene regions (e.g., ANK1 , BIN1 , RHBDF2 , SPG7, PODXL ) were significantly associated with amyloid load. DNA methylation in some regions was associated with expression of nearby genes. Discussion Targeted methylation sequencing can validate previous EWAS loci and discover novel CpGs associated with AD pathology.
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