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Genome-wide association study in a Korean population identifies six novel susceptibility loci for rheumatoid arthritis
- Title
- Genome-wide association study in a Korean population identifies six novel susceptibility loci for rheumatoid arthritis
- Authors
- Kwon Y.-C.; Lim J.; Bang S.-Y.; Ha E.; Hwang M.Y.; Yoon K.; Choe J.-Y.; Yoo D.-H.; Lee S.-S.; Lee J.; Chung W.T.; Kim T.-H.; Sung Y.-K.; Shim S.-C.; Choi C.-B.; Jun J.-B.; Kang Y.M.; Shin J.-M.; Lee Y.-K.; Cho S.-K.; Kim B.-J.; Lee H.-S.; Kim K.; Bae S.-C.
- Ewha Authors
- 이지수
- SCOPUS Author ID
- 이지수
- Issue Date
- 2020
- Journal Title
- Annals of the Rheumatic Diseases
- ISSN
- 0003-4967
- Citation
- Annals of the Rheumatic Diseases vol. 79, no. 11, pp. 1438 - 1445
- Keywords
- arthritis; autoimmune diseases; genetic; polymorphism; rheumatoid
- Publisher
- BMJ Publishing Group
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Objective Genome-wide association studies (GWAS) in rheumatoid arthritis (RA) have discovered over 100 RA loci, explaining patient-relevant RA pathogenesis but showing a large fraction of missing heritability. As a continuous effort, we conducted GWAS in a large Korean RA case-control population. Methods We newly generated genome-wide variant data in two independent Korean cohorts comprising 4068 RA cases and 36 487 controls, followed by a whole-genome imputation and a meta-analysis of the disease association results in the two cohorts. By integrating publicly available omics data with the GWAS results, a series of bioinformatic analyses were conducted to prioritise the RA-risk genes in RA loci and to dissect biological mechanisms underlying disease associations. Results We identified six new RA-risk loci (SLAMF6, CXCL13, SWAP70, NFKBIA, ZFP36L1 and LINC00158) with p meta <5×10 -8 and consistent disease effect sizes in the two cohorts. A total of 122 genes were prioritised from the 6 novel and 13 replicated RA loci based on physical distance, regulatory variants and chromatin interaction. Bioinformatics analyses highlighted potentially RA-relevant tissues (including immune tissues, lung and small intestine) with tissue-specific expression of RA-associated genes and suggested the immune-related gene sets (such as CD40 pathway, IL-21-mediated pathway and citrullination) and the risk-allele sharing with other diseases. Conclusion This study identified six new RA-associated loci that contributed to better understanding of the genetic aetiology and biology in RA. © Author(s) (or their employer(s)) 2020.
- DOI
- 10.1136/annrheumdis-2020-217663
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
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