Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci
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Kellis_Alzheimer's disease.pdf
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Author(s)
Srivastava, Gyan
Lunnon, Katie
Burgess, Jeremy
Yu, Lei
Ernst, Jason
McCabe, Cristin
Tang, Anna
Raj, Towfique
Replogle, Joseph
Brodeur, Wendy
Date Issued
August 2014
Journal
Nature Neuroscience
Publisher
Nature Publishing Group
Citation
De Jager, Philip L, Gyan Srivastava, Katie Lunnon, Jeremy Burgess, Leonard C Schalkwyk, Lei Yu, Matthew L Eaton, et al. “Alzheimer’s Disease: Early Alterations in Brain DNA Methylation at ANK1, BIN1, RHBDF2 and Other Loci.” Nat Neurosci 17, no. 9 (August 17, 2014): 1156–1163.
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Author's final manuscript
Abstract
We used a collection of 708 prospectively collected autopsied brains to assess the methylation state of the brain's DNA in relation to Alzheimer's disease (AD). We found that the level of methylation at 71 of the 415,848 interrogated CpGs was significantly associated with the burden of AD pathology, including CpGs in the ABCA7 and BIN1 regions, which harbor known AD susceptibility variants. We validated 11 of the differentially methylated regions in an independent set of 117 subjects. Furthermore, we functionally validated these CpG associations and identified the nearby genes whose RNA expression was altered in AD: ANK1, CDH23, DIP2A, RHBDF2, RPL13, SERPINF1 and SERPINF2. Our analyses suggest that these DNA methylation changes may have a role in the onset of AD given that we observed them in presymptomatic subjects and that six of the validated genes connect to a known AD susceptibility gene network.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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DOI of Published Version
https://doi.org/10.1038/nn.3786
