Genome-wide association study in a Korean population identifies six novel susceptibility loci for rheumatoid arthritis.
Genome-wide association study in a Korean population identifies six novel susceptibility loci for rheumatoid arthritis.
复制标题
DOI：
10.1136/annrheumdis-2020-217663
复制
发表时间：
2020-11
影响因子：
27.4
通讯作者：
Bae SC
中科院分区：
文献类型：
--
作者：
Kwon YC;Lim J;Bang SY;Ha E;Hwang MY;Yoon K;Choe JY;Yoo DH;Lee SS;Lee J;Chung WT;Kim TH;Sung YK;Shim SC;Choi CB;Jun JB;Kang YM;Shin JM;Lee YK;Cho SK;Kim BJ;Lee HS;Kim K;Bae SC
类风湿性关节炎（RA）的全基因组关联研究（GWAS）发现了100多个RA基因座，解释了患者相关的RA发病机制，但显示了很大一部分缺失的遗传性。作为一项持续的努力，我们在一个大型韩国RA病例对照人群中进行了GWAS。我们在两个独立的韩国队列中新生成了全基因组变异数据，包括4068例RA病例和36487例对照，随后进行了全基因组插补和两个队列中疾病关联结果的荟萃分析。通过将公开的组学数据与GWAS结果相结合，进行了一系列生物信息学分析，以优先考虑RA基因座中的RA风险基因，并剖析疾病相关的生物学机制。我们确定了6个新的RA风险位点（SLAMF 6，CXCL 13，SWAP 70，NFKBIA，ZFP 36 L1和LINC 00158），pmeta<5×10−8，两个队列中的疾病效应大小一致。根据物理距离、调节变体和染色质相互作用，从6个新的和13个复制的RA位点中总共优先考虑122个基因。生物信息学分析突出了RA相关基因的组织特异性表达的潜在RA相关组织（包括免疫组织、肺和小肠），并提示免疫相关基因集（如CD 40途径、IL-21介导的途径和瓜氨酸）和与其他疾病共享的风险等位基因。这项研究确定了六个新的RA相关基因座，有助于更好地了解RA的遗传病因学和生物学。
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. 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. 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. This study identified six new RA-associated loci that contributed to better understanding of the genetic aetiology and biology in RA.
登录
查看更多内容
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
DOI：
10.1002/art.39228
发表时间：
2015-10
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
Kim K;Jiang X;Cui J;Lu B;Costenbader KH;Sparks JA;Bang SY;Lee HS;Okada Y;Raychaudhuri S;Alfredsson L;Bae SC;Klareskog L;Karlson EW
通讯作者：
Karlson EW
简要报告：无关节炎受试者的气道异常和类风湿性关节炎相关自身抗体：早期损伤或自身免疫的起始部位？
影响因子：
--
作者：
Demoruelle, M. Kristen;Weisman, Michael H.;Simonian, Philip L.;Lynch, David A.;Sachs, Peter B.;Pedraza, Isabel F.;Harrington, Annie R.;Kolfenbach, Jason R.;Striebich, Christopher C.;Pham, Quyen N.;Strickland, Colin D.;Petersen, Brian D.;Parish, Mark C.;Derber, Lezlie A.;Norris, Jill M.;Holers, V. Michael;Deane, Kevin D.
通讯作者：
Deane, Kevin D.
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL