@article{6dd9204f8a0a496a9374d952f44d92fa,
title = "Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis",
abstract = "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.",
author = "Kazuyoshi Ishigaki and Saori Sakaue and Chikashi Terao and Yang Luo and Kyuto Sonehara and Kensuke Yamaguchi and Tiffany Amariuta and Too, {Chun Lai} and Laufer, {Vincent A} and Scott, {Ian C} and Sebastien Viatte and Meiko Takahashi and Koichiro Ohmura and Akira Murasawa and Motomu Hashimoto and Hiromu Ito and Mohammed Hammoudeh and Emadi, {Samar Al} and Masri, {Basel K} and Hussein Halabi and Humeira Badsha and Uthman, {Imad W} and Xin Wu and Li Lin and Ting Li and Darren Plant and Anne Barton and Gisela Orozco and Verstappen, {Suzanne M M} and John Bowes and MacGregor, {Alexander J} and Suguru Honda and Masaru Koido and Kohei Tomizuka and Yoichiro Kamatani and Hiroaki Tanaka and Eiichi Tanaka and Akari Suzuki and Yuichi Maeda and Kenichi Yamamoto and Satoru Miyawaki and Gang Xie and Jinyi Zhang and Amos, {Christopher I} and Edward Keystone and Gertjan Wolbink and {van der Horst-Bruinsma}, Irene and Jing Cui and Stephen Eyre and Soumya Raychaudhuri",
note = "{\textcopyright} 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
month = nov,
day = "4",
doi = "10.1038/s41588-022-01213-w",
language = "English",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Springer Nature",
}