Leiden University Scholarly Publications

Persistent URL of this record https://hdl.handle.net/1887/3505060

Documents

In Collections

This item can be found in the following collections:

Ishigaki, K.; Sakaue, S.; Terao, C.; Luo, Y.; Sonehara, K.; Yamaguchi, K.; ... ; BioBank Japan Project (2022)

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

Article / Letter to editor
Multi-ancestry genome-wide association analyses identify 124 risk loci for rheumatoid arthritis, of which 34 are novel. A polygenic risk score based on multi-ancestry data showed comparable performance between populations of European and East Asian ancestries.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 x 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...Show moreMulti-ancestry genome-wide association analyses identify 124 risk loci for rheumatoid arthritis, of which 34 are novel. A polygenic risk score based on multi-ancestry data showed comparable performance between populations of European and East Asian ancestries.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 x 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.Show less
All authors
Ishigaki, K.; Sakaue, S.; Terao, C.; Luo, Y.; Sonehara, K.; Yamaguchi, K.; Amariuta, T.; Too, C.L.; Laufer, V.A.; Scott, I.C.; Viatte, S.; Takahashi, M.; Ohmura, K.; Murasawa, A.; Hashimoto, M.; Ito, H.; Hammoudeh, M.; Emadi, S. al; Masri, B.K.; Halabi, H.; Badsha, H.; Uthman, I.W.; Wu, X.; Lin, L.; Li, T.; Plant, D.; Barton, A.; Orozco, G.; Verstappen, S.M.M.; Bowes, J.; MacGregor, A.J.; Honda, S.; Koido, M.; Tomizuka, K.; Kamatani, Y.; Tanaka, H.; Tanaka, E.; Suzuki, A.; Maeda, Y.; Yamamoto, K.; Miyawaki, S.; Xie, G.; Zhang, J.Y.; Amos, C.I.; Keystone, E.; Wolbink, G.; Horst-Bruinsma, I. van der; Cui, J.; Liao, K.P.; Carroll, R.J.; Lee, H.S.; Bang, S.Y.; Siminovitch, K.A.; Vries, N. de; Alfredsson, L.; Rantapaa-Dahlqvist, S.; Karlson, E.W.; Bae, S.C.; Kimberly, R.P.; Edberg, J.C.; Mariette, X.; Huizinga, T.; Dieude, P.; Schneider, M.; Kerick, M.; Denny, J.C.; Matsuda, K.; Matsuo, K.; Mimori, T.; Matsuda, F.; Fujio, K.; Tanaka, Y.; Kumanogoh, A.; Traylor, M.; Lewis, C.M.; Eyre, S.; Xu, H.J.; Saxena, R.; Arayssi, T.; Kochi, Y.; Ikari, K.; Harigai, M.; Gregersen, P.K.; Bridges, S.L.; Padyukov, L.; Martin, J.; Klareskog, L.; Okada, Y.; Raychaudhuri, S.; BioBank Japan Project
Date
2022-11-04
Journal
Nature Genetics
Volume
54
Issue
11
Pages
1640 - +
DOI
doi:10.1038/s41588-022-01213-w