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 Cho, Bong-Jo Kim, Hye‐Soon Lee, Kwang-Woo Kim, Sang‐Cheol Bae
Abstract
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: 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.