猪狩　勝則    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Endowed Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis.
Journal	Formal name：Nature genetics Abbreviation：Nat Genet ISSN code：15461718/10614036
Volume, Issue, Page	54(11),pp.1640-1651
Author and coauthor	Ishigaki K, Sakaue S, Terao C, Luo Y, Sonehara K, Yamaguchi K, Amariuta T, Too CL, Laufer VA, Scott IC,Viatte S,Takahashi M, Ohmura K, Murasawa A, Hashimoto M, Ito H, Hammoudeh M, Emadi SA, Masri BK, Halabi H, Badsha H, Uthman IW, Wu X, Lin L, Li T, Plant D, Barton A, Orozco G, Verstappen SMM, Bowes J, MacGregor AJ, Honda S, Koido M, Tomizuka K, Kamatani Y, Tanaka H, Tanaka E, Suzuki A, Maeda Y, Yamamoto K, Miyawaki S, Xie G, Zhang J, Amos CI, Keystone E, Wolbink G, van der Horst-Bruinsma I, Cui J, Liao KP, Carroll RJ, Lee HS, Bang SY, Siminovitch KA, de Vries N, Alfredsson L, Rantapää-Dahlqvist S, Karlson EW, Bae SC, Kimberly RP, Edberg JC, Mariette X, Huizinga T, Dieudé P, Schneider M, Kerick M, Denny JC; BioBank Japan Project, Matsuda K, Matsuo K, Mimori T, Matsuda F, Fujio K, Tanaka Y, Kumanogoh A, Traylor M, Lewis CM, Eyre S, Xu H, Saxena R, Arayssi T,Kochi Y,Ikari K,Harigai M,Gregersen PK,Yamamoto K,Louis Bridges S Jr,Padyukov L, Martin J,Klareskog L,Okada Y,Raychaudhuri S.
Publication date	2022/11
Summary	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.
DOI	10.1038/s41588-022-01213-w
PMID	36333501