A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk.
A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk.
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作者：
对基因网络和DNA序列变异的综合分析能够为常见疾病的病因学提供新的见解。在此，我们在大鼠的七种组织中使用全基因组整合方法来识别基因网络以及调控这些网络的基因位点。我们定义了一个由干扰素调节因子7（IRF7）驱动的炎症网络（iDIN），该网络富含病毒应答基因，是巨噬细胞的一种分子生物标志物，并且在多个组织中受到大鼠15q25染色体上一个位点的调控。在这个位点上，爱泼斯坦 - 巴尔病毒诱导基因2（Ebi2或Gpr183）——我们确定其位于巨噬细胞中且已知其可控制B淋巴细胞迁移——调控iDIN。与大鼠15q25同源的人类13q32位点控制着人类等效的iDIN，该网络在单核细胞中是保守的。对于与巨噬细胞相关的自身免疫性疾病1型糖尿病（T1D），iDIN基因相较于随机选择的免疫应答基因更有可能与T1D易感性相关（P = 8.85×10⁻⁶）。控制iDIN的人类位点在单核苷酸多态性rs9585056处与T1D风险相关（P = 7.0×10⁻¹⁰，优势比 = 1.15），该位点是此区域中与EBI2表达相关的五个单核苷酸多态性之一。这些数据表明IRF7网络基因及其调控位点在T1D的发病机制中起作用。
Combined analyses of gene networks and DNA sequence variation can provide new insights into the aetiology of common diseases. Here, we used integrated genome-wide approaches across seven rat tissues to identify gene networks and the loci underlying their regulation. We defined an interferon regulatory factor 7 (IRF7)-driven inflammatory network (iDIN) enriched for viral response genes, which represents a molecular biomarker for macrophages and was regulated in multiple tissues by a locus on rat chromosome 15q25. At this locus, Epstein-Barr virus induced gene 2 (Ebi2 or Gpr183), which we localised to macrophages and is known to control B lymphocyte migration, regulated the iDIN. The human chromosome 13q32 locus, orthologous to rat 15q25, controlled the human equivalent of iDIN, which was conserved in monocytes. For the macrophage-associated autoimmune disease type 1 diabetes (T1D) iDIN genes were more likely to associate with T1D susceptibility than randomly selected immune response genes (P = 8.85 × 10−6). The human locus controlling the iDIN, was associated with the risk of T1D at SNP rs9585056 (P = 7.0 × 10−10, odds ratio = 1.15), which was one of five SNPs in this region associated with EBI2 expression. These data implicate IRF7 network genes and their regulatory locus in the pathogenesis of T1D.
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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.
综合基因组方法暗示骨甘氨酸（OGN）在左心室肿块的调节中。
影响因子：
30.8
作者：
Petretto, Enrico;Sarwar, Rizwan;Grieve, Ian;Lu, Han;Kumaran, Mande K.;Muckett, Phillip J.;Mangion, Jonathan;Schroen, Blanche;Benson, Matthew;Punjabi, Prakash P.;Prasad, Sanjay K.;Pennell, Dudley J.;Kiesewetter, Chris;Tasheva, Elena S.;Corpuz, Lolita M.;Webb, Megan D.;Conrad, Gary W.;Kurtz, Theodore W.;Kren, Vladimir;Fischer, Judith;Hubner, Norbert;Pinto, Yigal M.;Pravenec, Michal;Aitman, Timothy J.;Cook, Stuart A.
通讯作者：
Cook, Stuart A.
影响因子：
7
作者：
Atanur, Santosh S.;Birol, Inanc;Aitman, Timothy J.
通讯作者：
Aitman, Timothy J.
影响因子：
4.3
作者：
Petretto E;Bottolo L;Langley SR;Heinig M;McDermott-Roe C;Sarwar R;Pravenec M;Hübner N;Aitman TJ;Cook SA;Richardson S
通讯作者：
Richardson S
影响因子：
30.8
作者：
Yvert, G;Brem, RB;Kruglyak, L
通讯作者：
Kruglyak, L