作者
Kazuyoshi Ishigaki, Saori Sakaue, Chikashi Terao, Yang Luo, Kyuto Sonehara, Kensuke Yamaguchi, Tiffany Amariuta, Chun Lai Too, Vincent A Laufer, Ian C Scott, Sebastien Viatte, Meiko Takahashi, Koichiro Ohmura, Akira Murasawa, Motomu Hashimoto, Hiromu Ito, Mohammed Hammoudeh, Samar Al Emadi, Basel K Masri, Hussein Halabi, Humeira Badsha, Imad W Uthman, Xin Wu, Li Lin, Ting Li, Darren Plant, Anne Barton, Gisela Orozco, Suzanne MM Verstappen, John Bowes, Alexander J MacGregor, Suguru Honda, Masaru Koido, Kohei Tomizuka, Yoichiro Kamatani, Hiroaki Tanaka, Eiichi Tanaka, Akari Suzuki, Yuichi Maeda, Kenichi Yamamoto, Satoru Miyawaki, Gang Xie, Jinyi Zhang, Christopher I Amos, Edward Keystone, Gertjan Wolbink, Irene Van der Horst-Bruinsma, Jing Cui, Katherine P Liao, Robert J Carroll, Hye-Soon Lee, So-Young Bang, Katherine A Siminovitch, Niek de Vries, Lars Alfredsson, Solbritt Rantapää-Dahlqvist, Elizabeth W Karlson, Sang-Cheol Bae, Robert P Kimberly, Jeffrey C Edberg, Xavier Mariette, Tom Huizinga, Philippe Dieudé, Matthias Schneider, Martin Kerick, Joshua C Denny, BioBank Japan Project, Koichi Matsuda, Keitaro Matsuo, Tsuneyo Mimori, Fumihiko Matsuda, Keishi Fujio, Yoshiya Tanaka, Atsushi Kumanogoh, Matthew Traylor, Cathryn M Lewis, Stephen Eyre, Huji Xu, Richa Saxena, Thurayya Arayssi, Yuta Kochi, Katsunori Ikari, Masayoshi Harigai, Peter K Gregersen, Kazuhiko Yamamoto, S Louis Bridges Jr, Leonid Padyukov, Javier Martin, Lars Klareskog, Yukinori Okada, Soumya Raychaudhuri
发表日期
2022/11
期刊
Nature genetics
卷号
54
期号
11
页码范围
1640-1651
出版商
Nature Publishing Group US
简介
Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P < 5 × 10−8), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. Multi-ancestry fine-mapping identified putatively causal variants with biological insights (for example, LEF1). Moreover, PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance …
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K Ishigaki, S Sakaue, C Terao, Y Luo, K Sonehara… - Nature genetics, 2022