A meta-analysis of epigenome-wide association studies in Alzheimer's disease highlights novel differentially methylated loci across cortex

Smith, R. G.; Pishva, E.; Shireby, G.; Smith, A. R.; Roubroeks, J. A. Y.; Hannon, E.; Wheildon, G.; Mastroeni, D.; Gasparoni, G.; Riemenschneider, M.; Giese, A.; Sharp, A. J.; Schalkwyk, L.; Haroutunian, V.; Viechtbauer, W.; van den Hove, D. L. A.; Weedon, M.; Brokaw, D.; Francis, P. T.; Thomas, A. J.; Love, S.; Morgan, K.; Walter, J.; Coleman, P. D.; Bennett, D. A.; De Jager, P. L.; Mill, J.; Lunnon, K.

URI

https://rde.dspace-express.com/handle/11287/621989

Author

Smith, R. G.

Pishva, E.

Shireby, G.

Smith, A. R.

Roubroeks, J. A. Y.

Hannon, E.

Wheildon, G.

Mastroeni, D.

Gasparoni, G.

Riemenschneider, M.

Giese, A.

Sharp, A. J.

Schalkwyk, L.

Haroutunian, V.

Viechtbauer, W.

van den Hove, D. L. A.

Weedon, M.

Brokaw, D.

Francis, P. T.

Thomas, A. J.

Love, S.

Morgan, K.

Walter, J.

Coleman, P. D.

Bennett, D. A.

De Jager, P. L.

Mill, J.

Lunnon, K.

Date

2021-06-10

Journal

Nature Communications

Type

Meta-Analysis

Publisher

Nature

DOI

10.1038/s41467-021-23243-4

Rights

Metadata

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Abstract

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/ ).

Citation

Smith, R. G., Pishva, E., Shireby, G., Smith, A. R., Roubroeks, J. A. Y., Hannon, E., Wheildon, G., Mastroeni, D., Gasparoni, G., Riemenschneider, M., Giese, A., Sharp, A. J., Schalkwyk, L., Haroutunian, V., Viechtbauer, W., van den Hove, D. L. A., Weedon, M., Brokaw, D., Francis, P. T., Thomas, A. J., Love, S., Morgan, K., Walter, J., Coleman, P. D., Bennett, D. A., De Jager, P. L., Mill, J. and Lunnon, K. (2021) 'A meta-analysis of epigenome-wide association studies in Alzheimer's disease highlights novel differentially methylated loci across cortex', Nature Communications, 12(1), pp. 3517.

Publisher URL

https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/34112773/

Note

This article is freely available online. Click on the 'Additional Link' above to access the full-text via the publisher's site.