Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers.
Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers.
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DOI：
10.1038/ng.3245
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发表时间：
2015-04
期刊：
影响因子：
30.8
通讯作者：
Rich, Stephen S.
中科院分区：
文献类型：
--
作者：
Onengut-Gumuscu, Suna;Chen, Wei-Min;Burren, Oliver;Cooper, Nick J.;Quinlan, Aaron R.;Mychaleckyj, Josyf C.;Farber, Emily;Bonnie, Jessica K.;Szpak, Michal;Schofield, Ellen;Achuthan, Premanand;Guo, Hui;Fortune, Mary D.;Stevens, Helen;Walker, Neil M.;Ward, Lucas D.;Kundaje, Anshul;Kellis, Manolis;Daly, Mark J.;Barrett, Jeffrey C.;Cooper, Jason D.;Deloukas, Panos;Todd, John A.;Wallace, Chris;Concannon, Patrick;Rich, Stephen S.
1型糖尿病（T1 D）的遗传研究已经确定了50个易感区域（www.T1DBase.org），揭示了导致风险的主要途径，其中一些基因座在免疫疾病中共享。为了使自身免疫性疾病之间的遗传比较尽可能提供信息，开发了一种密集的基因分型阵列，即免疫芯片，从中鉴定出四个新的T1 D区域（P < 5 × 10−8）。对15种免疫疾病的比较分析（www.ImmunoBase.org）显示，T1 D在遗传上与其他自身抗体阳性疾病更相似，最显著的是幼年特发性关节炎，最不明显的是溃疡性结肠炎，并为另外三个新的T1 D位点提供了支持。使用贝叶斯方法，我们定义了T1 D SNP的可信集。这些T1 D SNPs定位于胸腺、T和B细胞以及CD 34+干细胞中有活性的增强子序列。现在可以在这些细胞类型中分析增强子-启动子相互作用，以确定哪些特定基因和调控序列是因果关系。
Genetic studies of type 1 diabetes (T1D) have identified 50 susceptibility regions (www.T1DBase.org) revealing major pathways contributing to risk, with some loci shared across immune disorders. In order to make genetic comparisons across autoimmune disorders as informative as possible a dense genotyping array, the ImmunoChip, was developed, from which four novel T1D regions were identified (P < 5 × 10−8). A comparative analysis with 15 immune diseases (www.ImmunoBase.org) revealed that T1D is more similar genetically to other autoantibody-positive diseases, most significantly to juvenile idiopathic arthritis and least to ulcerative colitis, and provided support for three additional novel T1D loci. Using a Bayesian approach, we defined credible sets for the T1D SNPs. These T1D SNPs localized to enhancer sequences active in thymus, T and B cells, and CD34+ stem cells. Enhancer-promoter interactions can now be analyzed in these cell types to identify which particular genes and regulatory sequences are causal.
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DOI：
10.1177/1740774510373497
发表时间：
2010
期刊：
Clinical trials (London, England)
影响因子：
--
作者：
Hilner JE;Perdue LH;Sides EG;Pierce JJ;Wägner AM;Aldrich A;Loth A;Albret L;Wagenknecht LE;Nierras C;Akolkar B;T1DGC
通讯作者：
T1DGC
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.5
作者：
Manichaikul A;Palmas W;Rodriguez CJ;Peralta CA;Divers J;Guo X;Chen WM;Wong Q;Williams K;Kerr KF;Taylor KD;Tsai MY;Goodarzi MO;Sale MM;Diez-Roux AV;Rich SS;Rotter JI;Mychaleckyj JC
通讯作者：
Mychaleckyj JC
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：
30.8
作者：
Fairfax, Benjamin P.;Makino, Seiko;Radhakrishnan, Jayachandran;Plant, Katharine;Leslie, Stephen;Dilthey, Alexander;Ellis, Peter;Langford, Cordelia;Vannberg, Fredrik O.;Knight, Julian C.
通讯作者：
Knight, Julian C.