Epigenome-wide association study of human frontal cortex identifies differential methylation in Lewy body pathology

The goal of the study was to investigate if DNA methylation is associated with Lewy body pathology in human brain tissue. The Illumina Infinium MethylationEPIC Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs in postmortem human frontal cortex samples from European donors in the Netherlands Brain Bank. Following quality checks, sample filtering and normalization, association between CpG methylation and Braak alpha-synuclein stage was assessed using linear models. Bisulphite converted DNA from 492 samples including 453 unique donors and 39 technical replicates were hybridised to the Illumina Infinium MethylationEPIC Beadchip v. 1.0

本研究旨在探究人类脑组织中的DNA甲基化（DNA methylation）是否与路易体病理（Lewy body pathology）存在关联。本研究采用Illumina Infinium MethylationEPIC Beadchip芯片，对荷兰脑库（Netherlands Brain Bank）中欧洲供体的死后人类额叶皮层样本的约85万个CpG（CpG）位点的DNA甲基化谱进行了获取。经质量控制、样本筛选及标准化处理后，本研究通过线性模型评估了CpG甲基化与布拉克α-突触核蛋白分期（Braak alpha-synuclein stage）之间的关联。本研究共对492份样本的亚硫酸氢盐转化DNA（bisulphite converted DNA）进行了芯片杂交，其中包含453名独立供体样本与39份技术重复样本，所用芯片为Illumina Infinium MethylationEPIC Beadchip v.1.0。