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Integrated DNA Methylation/RNA Profiling in Middle Temporal Gyrus of Alzheimer’s Disease
Alzheimer’s disease is a neurodegenerative disorder clinically defined by gradual cognitive impairment and alteration in executive function. We conducted an epigenome-wide association study (EWAS) of a clinically and neuropathologically characterized cohort of 296 brains, including Alzheimer’s disea...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10287777/ https://www.ncbi.nlm.nih.gov/pubmed/36596913 http://dx.doi.org/10.1007/s10571-022-01307-3 |
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author | Piras, Ignazio S. Brokaw, Danielle Kong, Yinfei Weisenberger, Daniel J. Krate, Jonida Delvaux, Elaine Mahurkar, Swapna Blattler, Adam Siegmund, Kimberly D. Sue, Lucia Serrano, Geidy E. Beach, Thomas G. Laird, Peter W. Huentelman, Matthew J. Coleman, Paul D. |
author_facet | Piras, Ignazio S. Brokaw, Danielle Kong, Yinfei Weisenberger, Daniel J. Krate, Jonida Delvaux, Elaine Mahurkar, Swapna Blattler, Adam Siegmund, Kimberly D. Sue, Lucia Serrano, Geidy E. Beach, Thomas G. Laird, Peter W. Huentelman, Matthew J. Coleman, Paul D. |
author_sort | Piras, Ignazio S. |
collection | PubMed |
description | Alzheimer’s disease is a neurodegenerative disorder clinically defined by gradual cognitive impairment and alteration in executive function. We conducted an epigenome-wide association study (EWAS) of a clinically and neuropathologically characterized cohort of 296 brains, including Alzheimer’s disease (AD) and non-demented controls (ND), exploring the relationship with the RNA expression from matched donors. We detected 5246 CpGs and 832 regions differentially methylated, finding overlap with previous EWAS but also new associations. CpGs previously identified in ANK1, MYOC, and RHBDF2 were differentially methylated, and one of our top hits (GPR56) was not previously detected. ANK1 was differentially methylated at the region level, along with APOE and RHBDF2. Only a small number of genes showed a correlation between DNA methylation and RNA expression statistically significant. Multiblock partial least-squares discriminant analysis showed several CpG sites and RNAs discriminating AD and ND (AUC = 0.908) and strongly correlated with each other. Furthermore, the CpG site cg25038311 was negatively correlated with the expression of 22 genes. Finally, with the functional epigenetic module analysis, we identified a protein–protein network characterized by inverse RNA/DNA methylation correlation and enriched for “Regulation of insulin-like growth factor transport”, with IGF1 as the hub gene. Our results confirm and extend the previous EWAS, providing new information about a brain region not previously explored in AD DNA methylation studies. The relationship between DNA methylation and gene expression is not significant for most of the genes in our sample, consistently with the complexities in the gene expression regulation. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10571-022-01307-3. |
format | Online Article Text |
id | pubmed-10287777 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-102877772023-06-24 Integrated DNA Methylation/RNA Profiling in Middle Temporal Gyrus of Alzheimer’s Disease Piras, Ignazio S. Brokaw, Danielle Kong, Yinfei Weisenberger, Daniel J. Krate, Jonida Delvaux, Elaine Mahurkar, Swapna Blattler, Adam Siegmund, Kimberly D. Sue, Lucia Serrano, Geidy E. Beach, Thomas G. Laird, Peter W. Huentelman, Matthew J. Coleman, Paul D. Cell Mol Neurobiol Original Research Alzheimer’s disease is a neurodegenerative disorder clinically defined by gradual cognitive impairment and alteration in executive function. We conducted an epigenome-wide association study (EWAS) of a clinically and neuropathologically characterized cohort of 296 brains, including Alzheimer’s disease (AD) and non-demented controls (ND), exploring the relationship with the RNA expression from matched donors. We detected 5246 CpGs and 832 regions differentially methylated, finding overlap with previous EWAS but also new associations. CpGs previously identified in ANK1, MYOC, and RHBDF2 were differentially methylated, and one of our top hits (GPR56) was not previously detected. ANK1 was differentially methylated at the region level, along with APOE and RHBDF2. Only a small number of genes showed a correlation between DNA methylation and RNA expression statistically significant. Multiblock partial least-squares discriminant analysis showed several CpG sites and RNAs discriminating AD and ND (AUC = 0.908) and strongly correlated with each other. Furthermore, the CpG site cg25038311 was negatively correlated with the expression of 22 genes. Finally, with the functional epigenetic module analysis, we identified a protein–protein network characterized by inverse RNA/DNA methylation correlation and enriched for “Regulation of insulin-like growth factor transport”, with IGF1 as the hub gene. Our results confirm and extend the previous EWAS, providing new information about a brain region not previously explored in AD DNA methylation studies. The relationship between DNA methylation and gene expression is not significant for most of the genes in our sample, consistently with the complexities in the gene expression regulation. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10571-022-01307-3. Springer US 2023-01-03 2023 /pmc/articles/PMC10287777/ /pubmed/36596913 http://dx.doi.org/10.1007/s10571-022-01307-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Research Piras, Ignazio S. Brokaw, Danielle Kong, Yinfei Weisenberger, Daniel J. Krate, Jonida Delvaux, Elaine Mahurkar, Swapna Blattler, Adam Siegmund, Kimberly D. Sue, Lucia Serrano, Geidy E. Beach, Thomas G. Laird, Peter W. Huentelman, Matthew J. Coleman, Paul D. Integrated DNA Methylation/RNA Profiling in Middle Temporal Gyrus of Alzheimer’s Disease |
title | Integrated DNA Methylation/RNA Profiling in Middle Temporal Gyrus of Alzheimer’s Disease |
title_full | Integrated DNA Methylation/RNA Profiling in Middle Temporal Gyrus of Alzheimer’s Disease |
title_fullStr | Integrated DNA Methylation/RNA Profiling in Middle Temporal Gyrus of Alzheimer’s Disease |
title_full_unstemmed | Integrated DNA Methylation/RNA Profiling in Middle Temporal Gyrus of Alzheimer’s Disease |
title_short | Integrated DNA Methylation/RNA Profiling in Middle Temporal Gyrus of Alzheimer’s Disease |
title_sort | integrated dna methylation/rna profiling in middle temporal gyrus of alzheimer’s disease |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10287777/ https://www.ncbi.nlm.nih.gov/pubmed/36596913 http://dx.doi.org/10.1007/s10571-022-01307-3 |
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