Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases
| Autor: | Yukiko Iwasaki, Makoto Okazaki, Mai Okubo, Kazuhiko Yamamoto, Shuji Sumitomo, Hiroshi Kaneko, Satomi Kobayashi, Saeko Yamada, Chikashi Terao, Yasuo Nagafuchi, Nami Yabuki, Sohei Oyama, Shuji Akizuki, Tsuneyo Mimori, Haruka Tsuchiya, Koichiro Ohmura, Ken Yoshida, Kazuyoshi Ishigaki, Yukinori Okada, Ryochi Yoshida, Yuta Kochi, Tomohisa Okamura, Yusuke Takeshima, Mineto Ota, Keigo Setoguchi, Junko Maeda, Nobuhiro Ban, Yusuke Sugimori, Hironori Mutoh, Masato Okada, Daitaro Kurosaka, Keishi Fujio, Hiroaki Hatano, Hirofumi Shoda, Yumi Tsuchida, Haruyuki Yanaoka, Kosuke Matsuki, Hiroyuki Tsunoda, Hajime Yoshifuji, Masahiro Nakano, Harumi Shirai |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Cell type Quantitative Trait Loci Gene Expression Context (language use) Immunogenetics Disease Computational biology Biology Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Immune system Humans Genetic Predisposition to Disease Gene 030304 developmental biology Regulation of gene expression 0303 health sciences Whole Genome Sequencing Middle Aged Gene Expression Regulation Immune System Diseases Immune System Expression quantitative trait loci Female Transcriptome 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Cell. 184:3006-3021.e17 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2021.03.056 |
| Popis: | Summary Genetic studies have revealed many variant loci that are associated with immune-mediated diseases. To elucidate the disease pathogenesis, it is essential to understand the function of these variants, especially under disease-associated conditions. Here, we performed a large-scale immune cell gene-expression analysis, together with whole-genome sequence analysis. Our dataset consists of 28 distinct immune cell subsets from 337 patients diagnosed with 10 categories of immune-mediated diseases and 79 healthy volunteers. Our dataset captured distinctive gene-expression profiles across immune cell types and diseases. Expression quantitative trait loci (eQTL) analysis revealed dynamic variations of eQTL effects in the context of immunological conditions, as well as cell types. These cell-type-specific and context-dependent eQTLs showed significant enrichment in immune disease-associated genetic variants, and they implicated the disease-relevant cell types, genes, and environment. This atlas deepens our understanding of the immunogenetic functions of disease-associated variants under in vivo disease conditions. |
| Databáze: | OpenAIRE |
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