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Cross-tissue analysis of blood and brain epigenome-wide association studies in Alzheimer's disease.
- Source :
- Nature Communications; 8/18/2022, Vol. 13 Issue 1, p1-16, 16p
- Publication Year :
- 2022
-
Abstract
- To better understand DNA methylation in Alzheimer's disease (AD) from both mechanistic and biomarker perspectives, we performed an epigenome-wide meta-analysis of blood DNA methylation in two large independent blood-based studies in AD, the ADNI and AIBL studies, and identified 5 CpGs, mapped to the SPIDR, CDH6 genes, and intergenic regions, that are significantly associated with AD diagnosis. A cross-tissue analysis that combined these blood DNA methylation datasets with four brain methylation datasets prioritized 97 CpGs and 10 genomic regions that are significantly associated with both AD neuropathology and AD diagnosis. An out-of-sample validation using the AddNeuroMed dataset showed the best performing logistic regression model includes age, sex, immune cell type proportions, and methylation risk score based on prioritized CpGs in cross-tissue analysis (AUC = 0.696, 95% CI: 0.616 − 0.770, P-value = 2.78 × 10<superscript>−5</superscript>). Our study offers new insights into epigenetics in AD and provides a valuable resource for future AD biomarker discovery. DNA methylation differences in Alzheimer's disease have been previously reported, although the interpretation of the differences is unclear. Here, the authors performed epigenome-wide meta-analyses of DNA methylation in blood and brain, and developed a methylation-based risk prediction model for AD. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 13
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 158610615
- Full Text :
- https://doi.org/10.1038/s41467-022-32475-x