Pulse Brain · Growing Health Evidence Index
Tier 1 — Meta-analysis / systematic reviewPeer-reviewed

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

Kazuyoshi Ishigaki, Saori Sakaue, Chikashi Terao, Yang Luo, Kyuto Sonehara, Kensuke Yamaguchi, Tiffany Amariuta, Chun Lai Too, Vincent A. Laufer, Ian C. Scott, Sébastien Viatte, Meiko Takahashi, Koichiro Ohmura, Akira Murasawa, Motomu Hashimoto, Hiromu Ito, Samer Hammoudeh, Samar Al Emadi, Basel Masri, Hussein Halabi, Humeira Badsha, Imad Uthman, Xin Wu, Lin Li, Ting Li, Darren Plant, Anne Barton, Gisela Orozco, Suzanne Verstappen, John Bowes, Alex 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 Siminovitch, Niek de Vries, Lars Alfredsson, Solbritt Rantapää‐Dahlqvist, Elizabeth W. Karlson, Sang‐Cheol Bae, Robert P. Kimberly, Jeffrey C. Edberg, Xavier Mariette, T. Huizinga, Philippe Dieudé, Matthias Schneider, Martin Kerick, Joshua C. Denny, The 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, Leonid Padyukov, Javier Martı́n, Lars Klareskog, Yukinori Okada, Soumya Raychaudhuri

Nature Genetics · 2022

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Summary

This multi-ancestry genome-wide association study pooled genotype and phenotype data across geographically and ethnically diverse cohorts to identify genetic mechanisms underlying rheumatoid arthritis susceptibility. The research leveraged inclusive recruitment across multiple populations to reveal both ancestry-shared and ancestry-specific genetic signals, advancing understanding of disease aetiology. The findings suggest the value of diverse ancestry representation in genetic discovery for complex autoimmune diseases.

Regional applicability

The identified genetic variants and pathways may inform understanding of rheumatoid arthritis susceptibility in UK populations of European and other ancestries. Findings could support more equitable clinical risk prediction and mechanistic studies, though UK-specific validation and applicability to healthcare provision would require further research.

Key measures

Genetic associations (single-nucleotide polymorphisms, SNPs) with rheumatoid arthritis phenotype; effect sizes and significance thresholds across ancestry groups; biological pathway enrichment

Outcomes reported

The study identified novel genetic variants and biological pathways associated with rheumatoid arthritis susceptibility through genome-wide association analyses across multiple ancestral populations. It characterised both ancestry-specific and shared genetic contributions to disease risk.

Theme
Nutrition & health
Subject
Other / interdisciplinary
Study type
Research
Study design
Genome-wide association study (GWAS) meta-analysis
Source type
Peer-reviewed study
Status
Published
Geography
International
System type
Human clinical
DOI
10.1038/s41588-022-01213-w
Catalogue ID
SNmoi53hbn-hjeyhs

Topic tags

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