A genome-wide catalog of sites where peripheral DNA methylation reflects the brain
- 1Division of Geriatrics, Department of Family Medicine, School of Medicine, University of California, Irvine, Irvine, CA 92617, USA; Department of Psychiatry and
Abstract
Epigenetic studies of psychiatric and neurological disorders rely largely on peripheral tissues, yet where peripheral DNA methylation (DNAm) reflects the brain remains unclear. We generated a paired brain and peripheral DNAm dataset from 148 donors in three cohorts and combined it with five published cohorts for consensus brain-peripheral correlations. By cross-validation across cohorts, we defined brain epigenome shared sites (BrESS), more than 100,000 CpGs per tissue at which peripheral DNAm reproducibly predicts brain DNAm. BrESS lay at promoters active in both brain and periphery and in housekeeping genes, and most were not explained by genetic effects. BrESS did not contribute to the heritability of seven disorders, and CpGs from epigenome-wide association studies of these disorders were not enriched at BrESS. Peripheral DNAm reflects the brain mainly in a regulatory compartment shared across tissues, outside which disease signals largely lie, and BrESS separate peripheral signals attributable to the brain from others.
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BibTeX
@misc{nishitani2026genomewide,
title = {{A genome-wide catalog of sites where peripheral DNA methylation reflects the brain}},
author = {S. Nishitani and S. Han and T. Ishii and A. Shimura and N. J. Phuong and A. Kato and M. Chambers and T. Wang and M. Isozaki and Y. Higashino and T. Yamauchi and S. Kawajiri and H. Arishima and T. Kodera and H. Imoto and S. Nomura and K. Yamanishi and B. Aoyama and I. Genc and R. Sakuma and H. D. Nguyen and N. Gorantla and E. Ghasemi and A. Yao and S. Kurata and T. X. Fujisawa and P. R. Braun and T. Nagao and T. Yamanashi and A. Tomoda and K. Kikuta and T. Ooka and G. A. Grant and J. E. Hooper and M. A. Howard and H. Kawasaki and J. B. Potash and M. P. Snyder and G. Shinozaki},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.23.761276},
url = {https://www.biorxiv.org/content/10.64898/2026.10.23.761276v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A genome-wide catalog of sites where peripheral DNA methylation reflects the brain
AU - S. Nishitani
AU - S. Han
AU - T. Ishii
AU - A. Shimura
AU - N. J. Phuong
AU - A. Kato
AU - M. Chambers
AU - T. Wang
AU - M. Isozaki
AU - Y. Higashino
AU - T. Yamauchi
AU - S. Kawajiri
AU - H. Arishima
AU - T. Kodera
AU - H. Imoto
AU - S. Nomura
AU - K. Yamanishi
AU - B. Aoyama
AU - I. Genc
AU - R. Sakuma
AU - H. D. Nguyen
AU - N. Gorantla
AU - E. Ghasemi
AU - A. Yao
AU - S. Kurata
AU - T. X. Fujisawa
AU - P. R. Braun
AU - T. Nagao
AU - T. Yamanashi
AU - A. Tomoda
AU - K. Kikuta
AU - T. Ooka
AU - G. A. Grant
AU - J. E. Hooper
AU - M. A. Howard
AU - H. Kawasaki
AU - J. B. Potash
AU - M. P. Snyder
AU - G. Shinozaki
PY - 2026
DA - 2026/10/23
PB - bioRxiv
DO - 10.64898/2026.10.23.761276
UR - https://www.biorxiv.org/content/10.64898/2026.10.23.761276v1
AB - Epigenetic studies of psychiatric and neurological disorders rely largely on peripheral tissues, yet where peripheral DNA methylation (DNAm) reflects the brain remains unclear. We generated a paired brain and peripheral DNAm dataset from 148 donors in three cohorts and combined it with five published cohorts for consensus brain-peripheral correlations. By cross-validation across cohorts, we defined brain epigenome shared sites (BrESS), more than 100,000 CpGs per tissue at which peripheral DNAm reproducibly predicts brain DNAm. BrESS lay at promoters active in both brain and periphery and in housekeeping genes, and most were not explained by genetic effects. BrESS did not contribute to the heritability of seven disorders, and CpGs from epigenome-wide association studies of these disorders were not enriched at BrESS. Peripheral DNAm reflects the brain mainly in a regulatory compartment shared across tissues, outside which disease signals largely lie, and BrESS separate peripheral signals attributable to the brain from others.
ER -