2026-09-10 東京大学大学院医学系研究科, 大阪大学, 九州大学, 理化学研究所
研究の全体像
＜関連情報＞
- https://www.m.u-tokyo.ac.jp/news/PR/2026/release_20260910.pdf
- https://www.nature.com/articles/s41588-026-02741-5
多祖先ゲノムワイド関連解析およびマルチオミクス解析により、多発性硬化症の遺伝学における空間細胞学的特徴が解明される Multiancestry genome-wide association and multiomics analyses elucidate spatiocellular features of multiple sclerosis genetics
Rintaro Fujimoto,Kotaro Ogawa,Shinichi Namba,Yosuke Ogawa,Ryuya Edahiro,Kyuto Sonehara,Shiori Tagawa,Mitsuru Watanabe,Tomohiro Yata,Yuya Shirai,Yuji Yamamoto,Go Sato,Chifune Kai,Tatsuhiko Naito,Akiko Hosokawa,Mamoru Yamamoto,Japan MS/NMOSD Biobank,the BioBank Japan Project,Koichi Matsuda,Fumitaka Shimizu,Makoto Kinoshita,Masahito Mihara,Masayuki Nakamori,Yuko Shimizu,… Yukinori Okada
Nature Genetics Published:07 September 2026
DOI:https://doi.org/10.1038/s41588-026-02741-5
Abstract
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination disseminated in space and time. Here we performed a genome-wide association study (GWAS) using 688 MS cases and 205,199 controls from the Japanese population and identified significant associations in the major histocompatibility complex region and a population-specific risk variant in 11q24. Through cross-population GWAS meta-analyses using a total of 29,374 cases and 1,843,563 controls from 4 ancestral populations, we identified 22 novel susceptibility loci. Integration of GWAS and single-cell and single-nucleus RNA sequencing of peripheral blood mononuclear cells and subcortical lesions from patients with MS revealed enrichment of genetic risk factors for MS in CD4+ T helper cell lineage and regulatory T cells, as well as in endothelial cells. Furthermore, spatial transcriptomics of subcortical lesions demonstrated spatial and temporal heterogeneity in associations with MS genetic risk. Our study demonstrates the value of investigation of spatiocellular features of disease genetics across diverse populations and omics modalities.
