Genome-wide association study in a Korean population identifies six novel susceptibility loci for rheumatoid arthritis
- 주제(키워드) arthritis , autoimmune diseases , genetic , polymorphism , rheumatoid
- 등재 SCIE, SCOPUS
- OA유형 Green Published, hybrid
- 발행기관 BMJ Publishing Group
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000174768
- 본문언어 영어
- Published As http://dx.doi.org/10.1136/annrheumdis-2020-217663
- PubMed https://pubmed.ncbi.nlm.nih.gov/32723749
초록/요약
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.
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