PT  - JOURNAL ARTICLE
AU  - Young-Chang Kwon
AU  - Jiwoo Lim
AU  - So-Young Bang
AU  - Eunji Ha
AU  - Mi Yeong Hwang
AU  - Kyungheon Yoon
AU  - Jung-Yoon Choe
AU  - Dae-Hyun Yoo
AU  - Shin-Seok Lee
AU  - Jisoo Lee
AU  - Won Tae Chung
AU  - Tae-Hwan Kim
AU  - Yoon-Kyoung Sung
AU  - Seung-Cheol Shim
AU  - Chan-Bum Choi
AU  - Jae-Bum Jun
AU  - Young Mo Kang
AU  - Jung-Min Shin
AU  - Yeon-Kyung Lee
AU  - Soo-Kyung Cho
AU  - Bong-Jo Kim
AU  - Hye-Soon Lee
AU  - Kwangwoo Kim
AU  - Sang-Cheol Bae
TI  - Genome-wide association study in a Korean population identifies six novel susceptibility loci for rheumatoid arthritis
AID  - 10.1136/annrheumdis-2020-217663
DP  - 2020 Nov 01
TA  - Annals of the Rheumatic Diseases
PG  - 1438--1445
VI  - 79
IP  - 11
4099  - http://ard.bmj.com/content/79/11/1438.short
4100  - http://ard.bmj.com/content/79/11/1438.full
SO  - Ann Rheum Dis2020 Nov 01; 79
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.