TY - JOUR
T1 - A meta-analysis of epigenome-wide association studies in Alzheimer’s disease highlights novel differentially methylated loci across cortex
AU - Smith, Rebecca G.
AU - Pishva, Ehsan
AU - Shireby, Gemma
AU - Smith, Adam R.
AU - Roubroeks, Janou A.Y.
AU - Hannon, Eilis
AU - Wheildon, Gregory
AU - Mastroeni, Diego
AU - Gasparoni, Gilles
AU - Riemenschneider, Matthias
AU - Giese, Armin
AU - Sharp, Andrew J.
AU - Schalkwyk, Leonard
AU - Haroutunian, Vahram
AU - Viechtbauer, Wolfgang
AU - van den Hove, Daniel L.A.
AU - Weedon, Michael
AU - Brokaw, Danielle
AU - Francis, Paul T.
AU - Thomas, Alan J.
AU - Love, Seth
AU - Morgan, Kevin
AU - Walter, Jörn
AU - Coleman, Paul D.
AU - Bennett, David A.
AU - De Jager, Philip L.
AU - Mill, Jonathan
AU - Lunnon, Katie
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
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 = 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/).
AB - 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/).
UR - http://www.scopus.com/inward/record.url?scp=85107596838&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85107596838&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-23243-4
DO - 10.1038/s41467-021-23243-4
M3 - Article
C2 - 34112773
AN - SCOPUS:85107596838
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3517
ER -