Open AccessIntegrative analysis of DNA methylation and gene expression identifies genes associated with biological aging in Alzheimer's disease
Author(s) -
Kim BoHyun,
Vasanthakumar Aparna,
Li Qingqin S.,
Nudelman Kelly N.H.,
Risacher Shan L.,
Davis Justin W.,
Idler Kenneth,
Lee JongMin,
Seo Sang Won,
Waring Jeffrey F.,
Saykin Andrew J.,
Nho Kwangsik
Publication year - 2022
Publication title -
alzheimer's and dementia: diagnosis, assessment and disease monitoring
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.497
H-Index - 37
ISSN - 2352-8729
DOI - 10.1002/dad2.12354
Subject(s) - dna methylation , gene , disease , genetics , biology , gene expression , alzheimer's disease , methylation , computational biology , epigenetics , medicine
The acceleration of biological aging is a risk factor for Alzheimer's disease (AD). Here, we performed weighted gene co‐expression network analysis (WGCNA) to identify modules and dysregulated genesinvolved in biological aging in AD. Methods We performed WGCNA to identify modules associated with biological clocks and hub genes of the module with the highest module significance. In addition, we performed differential expression analysis and association analysis with AD biomarkers. Results WGCNA identified five modules associated with biological clocks, with the module designated as “purple” showing the strongest association. Functional enrichment analysis revealed that the purple module was related to cell migration and death. Ten genes were identified as hub genes in purple modules, of which CX3CR1 was downregulated in AD and low levels of CX3CR1 expression were associated with AD biomarkers. Conclusion Network analysis identified genes associated with biological clocks, which suggests the genetic architecture underlying biological aging in AD. HighlightsExamine links between Alzheimer's disease (AD) peripheral transcriptome and biological aging changes. Weighted gene co‐expression network analysis (WGCNA) found five modules related to biological aging. Among the hub genes of the module, CX3CR1 was downregulated in AD. The CX3CR1 expression level was associated with cognitive performance and brain atrophy.