TY - JOUR T1 - A meta-analysis of epigenome-wide association studies in Alzheimer’s disease highlights novel differentially methylated loci across cortex JF - bioRxiv DO - 10.1101/2020.02.28.957894 SP - 2020.02.28.957894 AU - Rebecca G. Smith AU - Ehsan Pishva AU - Gemma Shireby AU - Adam R. Smith AU - Janou A.Y. Roubroeks AU - Eilis Hannon AU - Gregory Wheildon AU - Diego Mastroeni AU - Gilles Gasparoni AU - Matthias Riemenschneider AU - Armin Giese AU - Andrew J. Sharp AU - Leonard Schalkwyk AU - Vahram Haroutunian AU - Wolfgang Viechtbauer AU - Daniel L.A. van den Hove AU - Michael Weedon AU - Danielle Brokaw AU - Paul T. Francis AU - Alan J Thomas AU - Seth Love AU - Kevin Morgan AU - Jörn Walter AU - Paul D. Coleman AU - David A. Bennett AU - Philip L. De Jager AU - Jonathan Mill AU - Katie Lunnon Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/04/02/2020.02.28.957894.abstract N2 - 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=1,453 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=1,408 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/).Competing Interest StatementThe authors have declared no competing interest. ER -