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DOI 10.1038/s41588-022-01213-w

Медицинская библиотека · Nature genetics · 2022

Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis.

Ishigaki Kazuyoshi, Sakaue Saori, Terao Chikashi, Luo Yang, Sonehara Kyuto, Yamaguchi Kensuke, Amariuta Tiffany, Too Chun Lai, Laufer Vincent A, Scott Ian C, Viatte Sebastien, Takahashi Meiko, Ohmura Koichiro, Murasawa Akira, Hashimoto Motomu, Ito Hiromu, Hammoudeh Mohammed, Emadi Samar Al, Masri Basel K, Halabi Hussein, Badsha Humeira, Uthman Imad W, Wu Xin, Lin Li, Li Ting, Plant Darren, Barton Anne, Orozco Gisela, Verstappen Suzanne M M, Bowes John, MacGregor Alexander J, Honda Suguru, Koido Masaru, Tomizuka Kohei, Kamatani Yoichiro, Tanaka Hiroaki, Tanaka Eiichi, Suzuki Akari, Maeda Yuichi, Yamamoto Kenichi, Miyawaki Satoru, Xie Gang, Zhang Jinyi, Amos Christopher I, Keystone Edward, Wolbink Gertjan, van der Horst-Bruinsma Irene, Cui Jing, Liao Katherine P, Carroll Robert J, Lee Hye-Soon, Bang So-Young, Siminovitch Katherine A, de Vries Niek, Alfredsson Lars, Rantapää-Dahlqvist Solbritt, Karlson Elizabeth W, Bae Sang-Cheol, Kimberly Robert P, Edberg Jeffrey C, Mariette Xavier, Huizinga Tom, Dieudé Philippe, Schneider Matthias, Kerick Martin, Denny Joshua C, BioBank Japan Project, Matsuda Koichi, Matsuo Keitaro, Mimori Tsuneyo, Matsuda Fumihiko, Fujio Keishi, Tanaka Yoshiya, Kumanogoh Atsushi, Traylor Matthew, Lewis Cathryn M, Eyre Stephen, Xu Huji, Saxena Richa, Arayssi Thurayya, Kochi Yuta, Ikari Katsunori, Harigai Masayoshi, Gregersen Peter K, Yamamoto Kazuhiko, Louis Bridges S, Padyukov Leonid, Martin Javier, Klareskog Lars, Okada Yukinori, Raychaudhuri Soumya

МетаанализСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

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 between populations of European and East Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA.

Для цитирования: Ishigaki Kazuyoshi, Sakaue Saori, Terao Chikashi, Luo Yang, Sonehara Kyuto, Yamaguchi Kensuke, Amariuta Tiffany, Too Chun Lai, Laufer Vincent A, Scott Ian C, Viatte Sebastien, Takahashi Meiko, Ohmura Koichiro, Murasawa Akira, Hashimoto Motomu, Ito Hiromu, Hammoudeh Mohammed, Emadi Samar Al, Masri Basel K, Halabi Hussein, Badsha Humeira, Uthman Imad W, Wu Xin, Lin Li, Li Ting, Plant Darren, Barton Anne, Orozco Gisela, Verstappen Suzanne M M, Bowes John, MacGregor Alexander J, Honda Suguru, Koido Masaru, Tomizuka Kohei, Kamatani Yoichiro, Tanaka Hiroaki, Tanaka Eiichi, Suzuki Akari, Maeda Yuichi, Yamamoto Kenichi, Miyawaki Satoru, Xie Gang, Zhang Jinyi, Amos Christopher I, Keystone Edward, Wolbink Gertjan, van der Horst-Bruinsma Irene, Cui Jing, Liao Katherine P, Carroll Robert J, Lee Hye-Soon, Bang So-Young, Siminovitch Katherine A, de Vries Niek, Alfredsson Lars, Rantapää-Dahlqvist Solbritt, Karlson Elizabeth W, Bae Sang-Cheol, Kimberly Robert P, Edberg Jeffrey C, Mariette Xavier, Huizinga Tom, Dieudé Philippe, Schneider Matthias, Kerick Martin, Denny Joshua C, BioBank Japan Project, Matsuda Koichi, Matsuo Keitaro, Mimori Tsuneyo, Matsuda Fumihiko, Fujio Keishi, Tanaka Yoshiya, Kumanogoh Atsushi, Traylor Matthew, Lewis Cathryn M, Eyre Stephen, Xu Huji, Saxena Richa, Arayssi Thurayya, Kochi Yuta, Ikari Katsunori, Harigai Masayoshi, Gregersen Peter K, Yamamoto Kazuhiko, Louis Bridges S, Padyukov Leonid, Martin Javier, Klareskog Lars, Okada Yukinori, Raychaudhuri Soumya. Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis.. Nature genetics. 2022. DOI: 10.1038/s41588-022-01213-w.

Предметные рубрики MeSH

HumansGenome-Wide Association StudyGenetic Predisposition to DiseasePolymorphism, Single NucleotideAsian PeopleArthritis, RheumatoidAdaptor Proteins, Signal Transducing
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