Ota Mineto, Nagafuchi Yasuo, Hatano Hiroaki, Ishigaki Kazuyoshi, Terao Chikashi, Takeshima Yusuke, Yanaoka Haruyuki, Kobayashi Satomi, Okubo Mai, Shirai Harumi, Sugimori Yusuke, Maeda Junko, Nakano Masahiro, Yamada Saeko, Yoshida Ryochi, Tsuchiya Haruka, Tsuchida Yumi, Akizuki Shuji, Yoshifuji Hajime, Ohmura Koichiro, Mimori Tsuneyo, Yoshida Ken, Kurosaka Daitaro, Okada Masato, Setoguchi Keigo, Kaneko Hiroshi, Ban Nobuhiro, Yabuki Nami, Matsuki Kosuke, Mutoh Hironori, Oyama Sohei, Okazaki Makoto, Tsunoda Hiroyuki, Iwasaki Yukiko, Sumitomo Shuji, Shoda Hirofumi, Kochi Yuta, Okada Yukinori, Yamamoto Kazuhiko, Okamura Tomohisa, Fujio Keishi
Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Cell. 2021 May 27;184(11):3006-3021.e17. doi: 10.1016/j.cell.2021.03.056. Epub 2021 May 1.
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.
基因研究已经揭示了许多与免疫介导疾病相关的变异位点。为了阐明疾病的发病机制,了解这些变异的功能至关重要,尤其是在疾病相关条件下。在这里,我们进行了大规模的免疫细胞基因表达分析,并结合全基因组序列分析。我们的数据集包括来自337名被诊断患有10种免疫介导疾病的患者和79名健康志愿者的28个不同的免疫细胞亚群。我们的数据集捕捉了不同免疫细胞类型和疾病的独特基因表达谱。表达数量性状位点(eQTL)分析揭示了在免疫条件以及细胞类型背景下eQTL效应的动态变化。这些细胞类型特异性和背景依赖性的eQTL在免疫疾病相关的遗传变异中表现出显著富集,并且它们涉及与疾病相关的细胞类型、基因和环境。这个图谱加深了我们对体内疾病条件下疾病相关变异的免疫遗传功能的理解。