Genome-wide association study in a Korean population identifies six novel susceptibility loci for rheumatoid arthritis

Young Chang Kwon, Jiwoo Lim, So Young Bang, Eunji Ha, Mi Yeong Hwang, Kyungheon Yoon, Jung Yoon Choe, Dae Hyun Yoo, Shin Seok Lee, Jisoo Lee, Won Tae Chung, Tae Hwan Kim, Yoon Kyoung Sung, Seung Cheol Shim, Chan Bum Choi, Jae Bum Jun, Young Mo Kang, Jung Min Shin, Yeon Kyung Lee, Soo Kyung ChoBong Jo Kim, Hye Soon Lee, Kwangwoo Kim, Sang Cheol Bae

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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.

Original languageEnglish
Pages (from-to)1438-1445
Number of pages8
JournalAnnals of the Rheumatic Diseases
Issue number11
StatePublished - 1 Nov 2020

Bibliographical note

Funding Information:
Funding This research was supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning (2017R1E1A1A01076388), the Korea Healthcare Technology R&D Project funded by the Ministry for Health and Welfare (HI15C3182) and Hanyang University Institute for Rheumatology Research. A part of genotype data was produced using the KoreanChip available through the K-CHIP consortium. KoreanChip was designed by Center for Genome Science, Korea National Institute of Health, Korea (4845–301, 3000–3031).

Publisher Copyright:
© Author(s) (or their employer(s)) 2020.


  • arthritis
  • autoimmune diseases
  • genetic
  • polymorphism
  • rheumatoid


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