期刊
ANNALS OF THE RHEUMATIC DISEASES
卷 79, 期 11, 页码 1438-1445出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/annrheumdis-2020-217663
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资金
- Basic Science Research Program through the National Research Foundation of Korea - Ministry of Science, ICT and Future Planning [2017R1E1A1A01076388]
- Korea Healthcare Technology R&D Project - Ministry for Health and Welfare [HI15C3182]
- Hanyang University Institute for Rheumatology Research
- National Research Foundation of Korea [2017R1E1A1A01076388] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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)<5x10(-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.
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