Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci

By Eli A. Stahl, Soumya Raychaudhuri, E. Remmers, Gang Xie, S. Eyre, Brian Thomson, Yonghong Li, F. Kurreeman, A. Zhernakova, A. Hinks and 58 more. Nature Genetics, 2010

1,367 citations recorded by the source corpus.

To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheumatoid arthritis cases and 8,806 controls. Of 34 SNPs selected for replication, 7 new rheumatoid arthritis risk alleles were identified at genome-wide significance (P < 5 × 10−8) in an analysis of all 41,282 samples. The associated SNPs are near genes of known immune function, including IL6ST, SPRED2, RBPJ, CCR6, IRF5 and PXK. We also refined associations at two established rheumatoid arthritis risk loci (IL2RA and CCL21) and confirmed the association at AFF3. These new associations bring the total number of confirmed rheumatoid arthritis risk loci to 31 among individuals of European ancestry. An additional 11 SNPs replicated at P < 0.05, many of which are validated autoimmune risk alleles, suggesting that most represent genuine rheumatoid arthritis risk alleles.

Subfields: Genetics, Pathology and Forensic Medicine, Rheumatology

View Paper: https://www.semanticscholar.org/paper/404c1a73884587ee2474408f18b3e80ffb5ed045

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. Peter M. Visscher
2. Michael E. Goddard
3. Naomi R. Wray
4. Jian Yang
5. Andriy Kryshtafovych
6. Joshua Charles Denny
7. Krzysztof Fidelis
8. Torsten Schwede

In Pathology and Forensic Medicine

1. S. Rose‐John
2. T. Hirano
3. Simon A. Jones
4. Dan R. Littman
5. Mark I. McCarthy

In Rheumatology

1. S. Rose‐John
2. Simon A. Jones
3. T. Hirano
4. J. Scheller

Citations in the corpus

• Five years of GWAS discovery. (2012, background): “g, the association of MTMR3 gene that was associated with lung cancer [31], Nephrophaty [32], and inflammatory bowel disease [33], [34] (Figure S17).”
• Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling. (2011, background): “These included gene products associated with STAT3 signaling/activity (IL6ST [GP130], SPRED2, CCR6), while a further suggestive risk allele was noted in the IL6R gene (125).”
• IL-6 in inflammation, autoimmunity and cancer (2020, background): “Genome-wide association studies (GWAS), meta-analysis, exome analysis and single nucleotide polymorphism (SNP) mapping have associated IL-6, IL-6R and gp130 with inflammatory diseases such as RA and coronary artery disease (263–269).”
• Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis (2013, background): “Many genetic susceptibility risk alleles have been discovered and validated (Stahl et al., 2010) but are insufficient to explain disease incidence.”
• Target highlights from the first post-PSI CASP experiment (CASP12, May–August 2016) (2017, positive): “Multiple genome-wide association studies (GWAS) revealed a correlation between single nucleotide polymorphisms (SNPs) in the protein coding and transcriptional regulatory regions of the neighboring GSDMA, GSDMB and ORDML3 genes with susceptibility to asthma,(57) type 1 diabetes,(58,59) Crohn’s disea”