Polygenic burdens on cell-specific pathways underlie the risk of rheumatoid arthritis

Kazuyoshi Ishigaki, Yuta Kochi, Akari Suzuki, Yumi Tsuchida, Haruka Tsuchiya, Shuji Sumitomo, Kensuke Yamaguchi, Yasuo Nagafuchi, Shinichiro Nakachi, Rika Kato, Keiichi Sakurai, Hirofumi Shoda, Katsunori Ikari, Atsuo Taniguchi, Hisashi Yamanaka, Fuyuki Miya, Tatsuhiko Tsunoda, Yukinori Okada, Yukihide Momozawa, Yoichiro KamataniRyo Yamada, Michiaki Kubo, Keishi Fujio, Kazuhiko Yamamoto

研究成果: Article

43 引用 (Scopus)

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Recent evidence suggests that a substantial portion of complex disease risk alleles modify gene expression in a cell-specific manner. To identify candidate causal genes and biological pathways of immune-related complex diseases, we conducted expression quantitative trait loci (eQTL) analysis on five subsets of immune cells (CD4 + T cells, CD8 + T cells, B cells, natural killer (NK) cells and monocytes) and unfractionated peripheral blood from 105 healthy Japanese volunteers. We developed a three-step analytical pipeline comprising (i) prediction of individual gene expression using our eQTL database and public epigenomic data, (ii) gene-level association analysis and (iii) prediction of cell-specific pathway activity by integrating the direction of eQTL effects. By applying this pipeline to rheumatoid arthritis data sets, we identified candidate causal genes and a cytokine pathway (upregulation of tumor necrosis factor (TNF) in CD4 + T cells). Our approach is an efficient way to characterize the polygenic contributions and potential biological mechanisms of complex diseases.

元の言語English
ページ(範囲)1120-1125
ページ数6
ジャーナルNature Genetics
49
発行部数7
DOI
出版物ステータスPublished - 01-07-2017

All Science Journal Classification (ASJC) codes

  • Genetics

フィンガープリント Polygenic burdens on cell-specific pathways underlie the risk of rheumatoid arthritis' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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    Ishigaki, K., Kochi, Y., Suzuki, A., Tsuchida, Y., Tsuchiya, H., Sumitomo, S., Yamaguchi, K., Nagafuchi, Y., Nakachi, S., Kato, R., Sakurai, K., Shoda, H., Ikari, K., Taniguchi, A., Yamanaka, H., Miya, F., Tsunoda, T., Okada, Y., Momozawa, Y., ... Yamamoto, K. (2017). Polygenic burdens on cell-specific pathways underlie the risk of rheumatoid arthritis. Nature Genetics, 49(7), 1120-1125. https://doi.org/10.1038/ng.3885