Cross-tissue analysis of blood and brain epigenome-wide association studies in Alzheimer’s disease

Tiago C. Silva, Juan I. Young, Lanyu Zhang, Lissette Gomez, Michael A. Schmidt, Achintya Varma, X. Steven Chen, Eden R. Martin and Lily Wang ()
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Tiago C. Silva: University of Miami, Miller School of Medicine
Juan I. Young: University of Miami, Miller School of Medicine
Lanyu Zhang: University of Miami, Miller School of Medicine
Lissette Gomez: University of Miami Miller School of Medicine
Michael A. Schmidt: University of Miami Miller School of Medicine
Achintya Varma: University of Miami Miller School of Medicine
X. Steven Chen: University of Miami, Miller School of Medicine
Eden R. Martin: University of Miami, Miller School of Medicine
Lily Wang: University of Miami, Miller School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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 × 10−5). Our study offers new insights into epigenetics in AD and provides a valuable resource for future AD biomarker discovery.

Date: 2022
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DOI: 10.1038/s41467-022-32475-x

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