Heinig, Matthias and Petretto, Enrico and Wallace, Chris and Bottolo, Leonardo and Rotival, Maxime and Lu, Han and Li, Yoyo and Sarwar, Rizwan and Langley, Sarah R. and Bauerfeind, Anja and Hummel, Oliver and Lee, Young-Ae and Paskas, Svetlana and Rintisch, Carola and Saar, Kathrin and Cooper, Jason and Buchan, Rachel and Gray, Elizabeth E. and Cyster, Jason G. and Erdmann, Jeanette and Hengstenberg, Christian and Maouche, Seraya and Ouwehand, Willem H. and Rice, Catherine M. and Samani, Nilesh J. and Schunkert, Heribert and Goodall, Alison H. and Schulz, Herbert and Roider, Helge G. and Vingron, Martin and Blankenberg, Stefan and Muenzel, Thomas and Zeller, Tanja and Szymczak, Silke and Ziegler, Andreas and Tiret, Laurence and Smyth, Deborah J. and Pravenec, Michal and Aitman, Timothy J. and Cambien, Francois and Clayton, David and Todd, John A. and Hubner, Norbert and Cook, Stuart A. (2010) A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk. NATURE, 467 (7314). pp. 460-464. ISSN 0028-0836, 1476-4687
Full text not available from this repository. (Request a copy)Abstract
Combined analyses of gene networks and DNA sequence variation can provide new insights into the aetiology of common diseases that may not be apparent from genome-wide association studies alone. Recent advances in rat genomics are facilitating systems-genetics approaches(1,2). Here we report the use of 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(3))-driven inflammatory network (IDIN) enriched for viral response genes, which represents a molecular biomarker for macrophages and which was regulated in multiple tissues by a locus on rat chromosome 15q25. We show that Epstein-Barr virus induced gene 2 (Ebi2, also known as Gpr183), which lies at this locus and controls B lymphocyte migration(4,5), is expressed in macrophages and regulates the IDIN. The human orthologous locus on chromosome 13q32 controlled the human equivalent of the IDIN, which was conserved in monocytes. IDIN genes were more likely to associate with susceptibility to type 1 diabetes (T1D)-amacrophage-associated autoimmune disease-than randomly selected immune response genes (P = 8.85 x 10(-6)). The human locus controlling the IDIN was associated with the risk of T1D at single nucleotide polymorphism rs9585056 (P = 7.0 x 10(-10); odds ratio, 1.15), which was one of five single nucleotide polymorphisms in this region associated with EBI2 (GPR183) expression. These data implicate IRF7 network genes and their regulatory locus in the pathogenesis of T1D.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; TRANSCRIPTION FACTORS; MOLECULAR NETWORKS; GENE-EXPRESSION; DISEASE; INFLAMMATION; RESPONSES; IFIH1; SNPS; RAT; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Jul 2020 06:48 |
| Last Modified: | 13 Jul 2020 06:48 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24165 |
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