Nature communications · 2021
A meta-analysis of epigenome-wide association studies in Alzheimer's disease highlights novel differentially methylated loci across cortex.
СтатьяМетаанализПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Smith Rebecca G, Pishva Ehsan, Shireby Gemma, Smith Adam R, Roubroeks Janou A Y, Hannon Eilis, Wheildon Gregory, Mastroeni Diego, Gasparoni Gilles, Riemenschneider Matthias, Giese Armin, Sharp Andrew J, Schalkwyk Leonard, Haroutunian Vahram, Viechtbauer Wolfgang, van den Hove Daniel L A, Weedon Michael, Brokaw Danielle, Francis Paul T, Thomas Alan J, Love Seth, Morgan Kevin, Walter Jörn, Coleman Paul D, Bennett David A, De Jager Philip L, Mill Jonathan, Lunnon Katie
Аннотация
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/ ).