Exploring the Genetic Predisposition to Epigenetic Changes in Alzheimer’s Disease
Alzheimer’s disease (AD) is a prevalent type of dementia in elderly populations with a significant genetic component. The accumulating evidence suggests that AD involves a reconfiguration of the epigenetic landscape, including DNA methylation, post-translational modification of histone proteins, and...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/9/7955 |
| _version_ | 1797602441200402432 |
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| author | Leonid O. Bryzgalov Elena E. Korbolina Tatiana I. Merkulova |
| author_facet | Leonid O. Bryzgalov Elena E. Korbolina Tatiana I. Merkulova |
| author_sort | Leonid O. Bryzgalov |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a prevalent type of dementia in elderly populations with a significant genetic component. The accumulating evidence suggests that AD involves a reconfiguration of the epigenetic landscape, including DNA methylation, post-translational modification of histone proteins, and chromatin remodeling. Along with environmental factors, individual specific genetic features play a considerable role in the formation of epigenetic architecture. In this study, we attempt to identify the non-coding regulatory SNPs (rSNPs) able to affect the epigenetic mechanisms in AD. To this end, the multi-omics approach is used. The GEO (Gene Expression Omnibus) available data (GSE153875) for AD patients and controls are integrated to reveal the rSNPs that display allele-specific features in both ChIP-seq profiles of four histone modifications and RNA-seq. Furthermore, we analyze the presence of rSNPs in the promoters of genes reported to be differentially expressed between AD and the normal brain (AD-related genes) and involved in epigenetic regulation according to the EpiFactors database. We also searched for the rSNPs in the promoters of the genes coding for transcription regulators of the identified AD-related genes. These regulators were selected based on the corresponding ChIP-seq peaks (ENCODE) in the promoter regions of these genes. Finally, we formed a panel of rSNPs localized to the promoters of genes that contribute to the epigenetic landscape in AD and, thus, to the genetic predisposition for this disease. |
| first_indexed | 2024-03-11T04:17:05Z |
| format | Article |
| id | doaj.art-5663097fa7544fbe983474d60779c247 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:17:05Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5663097fa7544fbe983474d60779c2472023-11-17T23:02:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01249795510.3390/ijms24097955Exploring the Genetic Predisposition to Epigenetic Changes in Alzheimer’s DiseaseLeonid O. Bryzgalov0Elena E. Korbolina1Tatiana I. Merkulova2The Federal Research Center Institute of Cytology and Genetics, The Siberian Branch of the Russian Academy of Science, 10 Lavrentyeva Prospekt, 630090 Novosibirsk, RussiaThe Federal Research Center Institute of Cytology and Genetics, The Siberian Branch of the Russian Academy of Science, 10 Lavrentyeva Prospekt, 630090 Novosibirsk, RussiaThe Federal Research Center Institute of Cytology and Genetics, The Siberian Branch of the Russian Academy of Science, 10 Lavrentyeva Prospekt, 630090 Novosibirsk, RussiaAlzheimer’s disease (AD) is a prevalent type of dementia in elderly populations with a significant genetic component. The accumulating evidence suggests that AD involves a reconfiguration of the epigenetic landscape, including DNA methylation, post-translational modification of histone proteins, and chromatin remodeling. Along with environmental factors, individual specific genetic features play a considerable role in the formation of epigenetic architecture. In this study, we attempt to identify the non-coding regulatory SNPs (rSNPs) able to affect the epigenetic mechanisms in AD. To this end, the multi-omics approach is used. The GEO (Gene Expression Omnibus) available data (GSE153875) for AD patients and controls are integrated to reveal the rSNPs that display allele-specific features in both ChIP-seq profiles of four histone modifications and RNA-seq. Furthermore, we analyze the presence of rSNPs in the promoters of genes reported to be differentially expressed between AD and the normal brain (AD-related genes) and involved in epigenetic regulation according to the EpiFactors database. We also searched for the rSNPs in the promoters of the genes coding for transcription regulators of the identified AD-related genes. These regulators were selected based on the corresponding ChIP-seq peaks (ENCODE) in the promoter regions of these genes. Finally, we formed a panel of rSNPs localized to the promoters of genes that contribute to the epigenetic landscape in AD and, thus, to the genetic predisposition for this disease.https://www.mdpi.com/1422-0067/24/9/7955Alzheimer’s diseaseepigeneticshistone modificationchromatin remodelingnon-coding regulatory SNPstranscription factors |
| spellingShingle | Leonid O. Bryzgalov Elena E. Korbolina Tatiana I. Merkulova Exploring the Genetic Predisposition to Epigenetic Changes in Alzheimer’s Disease International Journal of Molecular Sciences Alzheimer’s disease epigenetics histone modification chromatin remodeling non-coding regulatory SNPs transcription factors |
| title | Exploring the Genetic Predisposition to Epigenetic Changes in Alzheimer’s Disease |
| title_full | Exploring the Genetic Predisposition to Epigenetic Changes in Alzheimer’s Disease |
| title_fullStr | Exploring the Genetic Predisposition to Epigenetic Changes in Alzheimer’s Disease |
| title_full_unstemmed | Exploring the Genetic Predisposition to Epigenetic Changes in Alzheimer’s Disease |
| title_short | Exploring the Genetic Predisposition to Epigenetic Changes in Alzheimer’s Disease |
| title_sort | exploring the genetic predisposition to epigenetic changes in alzheimer s disease |
| topic | Alzheimer’s disease epigenetics histone modification chromatin remodeling non-coding regulatory SNPs transcription factors |
| url | https://www.mdpi.com/1422-0067/24/9/7955 |
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