Year: 2026
Type: preprint
Study design: Observational Study
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.
Authors: Shota Nishitani, Shizhong Han, Takaya Ishii, Akiyoshi Shimura, Nathan J. Phuong, Asahi Kato, Meagan Chambers, Tao Wang, Makoto Isozaki, Yoshifumi Higashino, Takahiro Yamauchi, Satoshi Kawajiri, Hidetaka Arishima, Toshiaki Kodera, Hirochika Imoto, Sadahiro Nomura, Kyosuke Yamanishi, Bun Aoyama, Ilgin Genc, Rika Sakuma, Hieu D. Nguyen, Nipun Gorantla, Elnaz Ghasemi, Akiko Yao, Sawa Kurata, Takashi X. Fujisawa, Patricia R. Braun, Takaaki Nagao, Takehiko Yamanashi, Akemi Tomoda, Kenichiro Kikuta, Tadao Ooka, Gerald A. Grant, Jody E. Hooper, Matthew A. Howard, Hiroto Kawasaki, James B. Potash, Michael P. Snyder, Gen Shinozaki
Institutions: Kanazawa University, University of Fukui, Chiba University, University of California, Irvine, Hamamatsu University School of Medicine, Stanford Medicine, Research Center for Child Mental Development, University of Fukui, University of Yamanashi, Stanford University, The University of Osaka, University of Iowa, Johns Hopkins University, Johns Hopkins Medicine, University of Iowa Health Care, Lieber Institute for Brain Development, Sumitomo Dainippon Pharma (Japan), Tokyo Medical University, Yamaguchi University, Yamaguchi University Hospital, Hyogo Medical University, National Hospital Organization Kochi National Hospital, Kochi Medical School Hospital, National Hospital Organization, Grinnell College, Toho University, Toho University Medical Center Sakura Hospital, Tottori University, Duke University, Duke Medical Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7223451804