Anti-citrullinated peptide/protein antibody (ACPA)-negative RA shares a large proportion of susceptibility loci with ACPA-positive RA: a meta-analysis of genome-wide association study in a Japanese population.
Anti-citrullinated peptide/protein antibody (ACPA)-negative RA shares a large proportion of susceptibility loci with ACPA-positive RA: a meta-analysis of genome-wide association study in a Japanese population.
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抗硝化肽/蛋白质抗体（ACPA）阴性RA与ACPA阳性RA共享很大比例的敏感位点：对日本人群中基因组关联研究的荟萃分析。
DOI：
10.1186/s13075-015-0623-4
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发表时间：
2015-04-18
影响因子：
4.9
通讯作者：
Matsuda F
中科院分区：
文献类型：
--
作者：
Terao C;Ohmura K;Kochi Y;Ikari K;Okada Y;Shimizu M;Nishina N;Suzuki A;Myouzen K;Kawaguchi T;Takahashi M;Takasugi K;Murasawa A;Mizuki S;Iwahashi M;Funahashi K;Natsumeda M;Furu M;Hashimoto M;Ito H;Fujii T;Ezawa K;Matsubara T;Takeuchi T;Kubo M;Yamada R;Taniguchi A;Yamanaka H;Momohara S;Yamamoto K;Mimori T;Matsuda F
虽然抗瓜氨酸肽/蛋白抗体（ACPA）阳性的类风湿关节炎（RA）的易感基因已经通过全基因组关联研究（GWAS）成功发现，但对ACPA阴性的类风湿关节炎的遗传背景知之甚少。我们旨在阐明acpa阴性RA的遗传背景。我们对GWAS进行了荟萃分析，包括670例acpa阴性RA和16,891例对照，1,948,138个标记，随后对916例和3,764例对照进行了前35个单核苷酸多态性（snp）的复制研究。采用反方差法评价总体效果。为了评估acpa阳性和阴性RA之间易感位点的重叠，比较了日本人群中21种RA易感标志物的比值比（ORs）。此外，通过GWAS荟萃分析中acpa阳性RA或acpa阴性RA的p值对snp进行分层，以解决是否也共享弱相关基因的问题。acpa阳性RA与acpa阴性RA亚群（类风湿因子（RF）阳性和RF阴性亚群）之间的相关性也得到了解决。人白细胞抗原（HLA）位点LEMD2中的Rs6904716与acpa阴性RA呈交界性相关（总体p = 5.7 × 10−8），其次是CSMD1中的rs6986423 （p = 2.4 × 10−6）和FCRL3中的rs17727339 （p = 1.4 × 10−5）。acpa阴性RA与acpa阳性RA在21个易感性snp和非hla snp上的ORs呈显著相关，p值远无显著性。这些与acpa阳性RA的显著相关性适用于acpa阴性rf阳性RA和acpa阴性rf阴性RA。相反，acpa阴性的两个亚群之间没有观察到正相关。许多易感位点在acpa阳性和阴性RA之间是共享的。本文的在线版本（doi:10.1186/s13075-015-0623-4）包含补充材料，授权用户可以使用。
Although susceptibility genes for anti-citrullinated peptide/protein antibodies (ACPA)-positive rheumatoid arthritis (RA) have been successfully discovered by genome-wide association studies (GWAS), little is known about the genetic background of ACPA-negative RA. We intended to elucidate genetic background of ACPA-negative RA. We performed a meta-analysis of GWAS comprising 670 ACPA-negative RA and 16,891 controls for 1,948,138 markers, followed by a replication study of the top 35 single nucleotide polymorphisms (SNPs) using 916 cases and 3,764 controls. Inverse-variance method was applied to assess overall effects. To assess overlap of susceptibility loci between ACPA-positive and -negative RA, odds ratios (ORs) of the 21 susceptibility markers to RA in Japanese were compared between the two subsets. In addition, SNPs were stratified by the p-values in GWAS meta-analysis for either ACPA-positive RA or ACPA-negative RA to address the question whether weakly-associated genes were also shared. The correlations between ACPA-positive RA and the subpopulations of ACPA-negative RA (rheumatoid factor (RF)-positive and RF-negative subsets) were also addressed. Rs6904716 in LEMD2 of the human leukocyte antigen (HLA) locus showed a borderline association with ACPA-negative RA (overall p = 5.7 × 10−8), followed by rs6986423 in CSMD1 (p = 2.4 × 10−6) and rs17727339 in FCRL3 (p = 1.4 × 10−5). ACPA-negative RA showed significant correlations of ORs with ACPA-positive RA for the 21 susceptibility SNPs and non-HLA SNPs with p-values far from significance. These significant correlations with ACPA-positive RA were true for ACPA-negative RF-positive and ACPA-negative RF-negative RA. On the contrary, positive correlations were not observed between the ACPA-negative two subpopulations. Many of the susceptibility loci were shared between ACPA-positive and -negative RA. The online version of this article (doi:10.1186/s13075-015-0623-4) contains supplementary material, which is available to authorized users.
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影响因子：
158.5
作者：
Remmers, Elaine F.;Plenge, Robert M.;Gregersen, Peter K.
通讯作者：
Gregersen, Peter K.
影响因子：
158.5
作者：
Plenge, Robert M.;Seielstad, Mark;Gregersen, Peter K.
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作者：
Han, Buhm;Diogo, Dorothee;Raychaudhuri, Soumya
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Raychaudhuri, Soumya
影响因子：
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作者：
Burgner D;Davila S;Breunis WB;Ng SB;Li Y;Bonnard C;Ling L;Wright VJ;Thalamuthu A;Odam M;Shimizu C;Burns JC;Levin M;Kuijpers TW;Hibberd ML;International Kawasaki Disease Genetics Consortium
通讯作者：
International Kawasaki Disease Genetics Consortium
影响因子：
4.4
作者：
Kraus, Damian M.;Elliott, Gary S.;Holers, V. Michael
通讯作者：
Holers, V. Michael