RT Journal Article
SR Electronic
T1 Genome-wide association study in a Korean population identifies six novel susceptibility loci for rheumatoid arthritis
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 1438
OP 1445
DO 10.1136/annrheumdis-2020-217663
VO 79
IS 11
A1 Young-Chang Kwon
A1 Jiwoo Lim
A1 So-Young Bang
A1 Eunji Ha
A1 Mi Yeong Hwang
A1 Kyungheon Yoon
A1 Jung-Yoon Choe
A1 Dae-Hyun Yoo
A1 Shin-Seok Lee
A1 Jisoo Lee
A1 Won Tae Chung
A1 Tae-Hwan Kim
A1 Yoon-Kyoung Sung
A1 Seung-Cheol Shim
A1 Chan-Bum Choi
A1 Jae-Bum Jun
A1 Young Mo Kang
A1 Jung-Min Shin
A1 Yeon-Kyung Lee
A1 Soo-Kyung Cho
A1 Bong-Jo Kim
A1 Hye-Soon Lee
A1 Kwangwoo Kim
A1 Sang-Cheol Bae
YR 2020
UL http://ard.bmj.com/content/79/11/1438.abstract
AB 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 pmeta<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.