Abstract
Epigenome-wide association studies (EWAS) assessing the link between DNA methylation (DNAm) and phenotypes related to structural brain measures, cognitive function, and neurodegenerative diseases are becoming increasingly more popular. Due to the inaccessibility of brain tissue in humans, several studies use peripheral tissues such as blood, buccal swabs, and saliva as surrogates. To aid the functional interpretation of EWAS findings in such settings, there is a need to assess the correlation of DNAm variability across tissues in the same individuals. In this study, we performed a correlation analysis between DNAm data of a total of n = 120 matched post-mortem buccal and prefrontal cortex samples. We identified nearly 25,000 (3% of approximately 730,000) cytosine-phosphate-guanine (CpG) sites showing significant (false discovery rate q < 0.05) correlations between buccal and PFC samples. Correlated CpG sites showed a preponderance to being located in promoter regions and showed a significant enrichment of being determined by genetic factors, i.e. methylation quantitative trait loci (mQTL), based on buccal and dorsolateral prefrontal cortex mQTL databases. Our novel buccal–brain DNAm correlation map will provide a valuable resource for future EWAS using buccal samples for studying DNAm effects on phenotypes relating to the brain. All correlation results are made freely available to the public online.
| Original language | English |
|---|---|
| Article number | 139 |
| Journal | Clinical Epigenetics |
| Volume | 14 |
| Issue number | 1 |
| ISSN | 1868-7075 |
| DOIs | |
| Publication status | Published - 12.2022 |
Funding
BTH has a family member who works at Novartis, and owns stock in Novartis; he serves on the SAB of Dewpoint and owns stock. He serves on a scientific advisory board or is a consultant for AbbVie, Avrobio, Axon, Biogen, BMS Cell Signaling, Genentech, Ionis, PPF, Novartis, Seer, Takeda, the US Dept of Justice, Vigil, Voyager. His laboratory is supported by Sponsored research agreements with Abbvie, F Prime, and research grants from the National Institutes of Health, Cure Alzheimer’s Fund, Tau Consortium, and the JPB Foundation. The other authors declare no conflict of interest. Open Access funding enabled and organized by Projekt DEAL. This work was supported by the Cure Alzheimer’s Fund (as part of the “CIRCUITS” consortium) to LB, Deutsche Forschungsgemeinschaft (DFG) and the National Science Foundation China (NSFC) as part of the Joint Sino-German research project (“MiRNet-AD”, #391523883) to LB, and by the EU Horizon 2020 Fund (as part of the “Lifebrain” consortium, #732592) to LB. The BASE-II research project (Co-PIs: Lars Bertram, Ilja Demuth, Denis Gerstorf, Ulman Lindenberger, Graham Pawelec, Elisabeth Steinhagen-Thiessen, and Gert G. Wagner) is supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) under grant numbers #16SV5536K, #16SV5537, #16SV5538, #16SV5837, #01UW0808, 01GL1716A, and 01GL1716B. The Massachusetts Alzheimer’s Disease Research Center is supported by the National Institute on Aging NIA (Grant P30AG062421). CML is supported by the Heisenberg Program of the DFG (LI 2654/4-1).
Research Areas and Centers
- Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)
DFG Research Classification Scheme
- 2.11-05 General Genetics and Functional Genome Biology
