Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis.
Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis.
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DOI：
10.1038/ng.2614
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发表时间：
2013-06
期刊：
影响因子：
30.8
通讯作者：
Thompson, Susan D.
中科院分区：
文献类型：
--
作者：
Hinks, Anne;Cobb, Joanna;Marion, Miranda C.;Prahalad, Sampath;Sudman, Marc;Bowes, John;Martin, Paul;Comeau, Mary E.;Sajuthi, Satria;Andrews, Robert;Brown, Milton;Chen, Wei-Min;Concannon, Patrick;Deloukas, Panos;Edkins, Sarah;Eyre, Stephen;Gaffney, Patrick M.;Guthery, Stephen L.;Guthridge, Joel M.;Hunt, Sarah E.;James, Judith A.;Keddache, Mehdi;Moser, Kathy L.;Nigrovic, Peter A.;Onengut-Gumuscu, Suna;Onslow, Mitchell L.;Rose, Carlos D.;Rich, Stephen S.;Steel, Kathryn J. A.;Wakeland, Edward K.;Wallace, Carol A.;Wedderburn, Lucy R.;Woo, Patricia;Bohnsack, John F.;Haas, Johannes Peter;Glass, David N.;Langefeld, Carl D.;Thomson, Wendy;Thompson, Susan D.
对 2816 名个体（包括幼年特发性关节炎 (JIA) 最常见亚型（少关节型和 RF 阴性多关节型）和 13056 个对照）的免疫芯片单核苷酸多态性 (SNP) 阵列进行分析，加强了与三个已知 JIA 风险位点（HLA、PTPN22 和 PTPN2）相关的证据，并已鉴定出 14 个位点 风险位点首次达到全基因组显着性（p < 5 × 10-8）。另外 11 个新区域显示出与 JIA 相关的提示性证据 (p < 1 × 10-6)。位点的密集作图和生物信息学分析已经细化了八个区域与一个基因的关联，突出了 JIA 疾病发病机制中的关键途径，包括 IL-2 途径。整个免疫芯片基因座、HLA 区域和前 27 个基因座 (p < 1 × 10-6) 分别解释了估计的 18%、13% 和 6% 的 JIA 风险。对免疫芯片数据集的分析是迄今为止调查的最大的 JIA 病例队列，为了解这种儿童自身免疫性疾病的遗传基础提供了新的见解。
Analysis of the ImmunoChip single nucleotide polymorphism (SNP) array in 2816 individuals, comprising the most common subtypes (oligoarticular and RF negative polyarticular) of juvenile idiopathic arthritis (JIA) and 13056 controls strengthens the evidence for association to three known JIA-risk loci (HLA, PTPN22 and PTPN2) and has identified fourteen risk loci reaching genome-wide significance (p < 5 × 10-8) for the first time. Eleven additional novel regions showed suggestive evidence for association with JIA (p < 1 × 10-6). Dense-mapping of loci along with bioinformatic analysis has refined the association to one gene for eight regions, highlighting crucial pathways, including the IL-2 pathway, in JIA disease pathogenesis. The entire ImmunoChip loci, HLA region and the top 27 loci (p < 1 × 10-6) explain an estimated 18%, 13% and 6% risk of JIA, respectively. Analysis of the ImmunoChip dataset, the largest cohort of JIA cases investigated to date, provides new insight in understanding the genetic basis for this childhood autoimmune disease.
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影响因子：
30.8
作者：
Barrett, Jeffrey C.;Clayton, David G.;Concannon, Patrick;Akolkar, Beena;Cooper, Jason D.;Erlich, Henry A.;Julier, Cecile;Morahan, Grant;Nerup, Jorn;Nierras, Concepcion;Plagnol, Vincent;Pociot, Flemming;Schuilenburg, Helen;Smyth, Deborah J.;Stevens, Helen;Todd, John A.;Walker, Neil M.;Rich, Stephen S.
通讯作者：
Rich, Stephen S.
影响因子：
--
作者：
Hinks, Anne;Ke, Xiayi;Barton, Anne;Eyre, Steve;Bowes, John;Worthington, Jane;Thompson, Susan D.;Langefeld, Carl D.;Glass, David N.;Thomson, Wendy
通讯作者：
Thomson, Wendy
影响因子：
27.4
作者：
Hinks, Anne;Eyre, Steve;Thomson, Wendy
通讯作者：
Thomson, Wendy
症状的持续时间与疾病严重程度在第一次出现到小儿风湿病学：儿童期关节炎前瞻性研究的结果。
影响因子：
5.5
作者：
Adib, N.;Hyrich, K.;Thornton, J.;Lunt, M.;Davidson, J.;Gardner-Medwin, J.;Foster, H.;Baildam, E.;Wedderburn, L.;Thomson, W.
通讯作者：
Thomson, W.
影响因子：
30.8
作者：
Jin Y;Birlea SA;Fain PR;Ferrara TM;Ben S;Riccardi SL;Cole JB;Gowan K;Holland PJ;Bennett DC;Luiten RM;Wolkerstorfer A;van der Veen JP;Hartmann A;Eichner S;Schuler G;van Geel N;Lambert J;Kemp EH;Gawkrodger DJ;Weetman AP;Taïeb A;Jouary T;Ezzedine K;Wallace MR;McCormack WT;Picardo M;Leone G;Overbeck A;Silverberg NB;Spritz RA
通讯作者：
Spritz RA