A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk
Open accessAbstract
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. 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)-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, 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)-a macrophage-associated autoimmune disease-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 single nucleotide polymorphism rs9585056 (P = 7.0 × 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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Integration of genetic information with network modeling has been used to highlight pathways that contribute to disease and to identify key drivers in biologic processes.
“Such integration of genetic information with network modeling has been used to highlight pathways that contribute to disease and to identify “key drivers” in biologic processes [72–74, 78].”
From Multi-omics approaches to disease (2017) · cites this paper as [78]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442 · see citing works
Self-citationIRF-7 is the master regulator of type-I interferon-dependent immune responses
Honda, K., Yanai, H., Negishi, H., Asagiri, M., Sato, M., Mizutani, T., Shimada, N., Ohba, Y., Takaoka, A., Yoshida, N., et al. (2005) · Nature · doi:10.1038/nature03464 · Cited by 2,229 · see citing works
Nathan, C., & Ding, A. (2010) · Cell · doi:10.1016/j.cell.2010.02.029 · Cited by 2,183 · see citing works
The Type 1 Diabetes Genetics Consortium, Barrett, J. C., Clayton, D. G., Concannon, P., Akolkar, B., Cooper, J. D., Erlich, H. A., Julier, C., Morahan, G., Nerup, J., et al. (2009) · Nature Genetics · doi:10.1038/ng.381 · Cited by 1,746 · see citing works
Self-citationGenetic Mapping in Human Disease
Altshuler, D., Daly, M. J., & Lander, E. S. (2008) · Science · doi:10.1126/science.1156409 · Cited by 1,452 · see citing works
Genetic Dissection of Transcriptional Regulation in Budding Yeast
Brem, R. B., Yvert, G., Clinton, R., & Kruglyak, L. (2002) · Science · doi:10.1126/science.1069516 · Cited by 1,392 · see citing works
Kawai, T., Sato, S., Ishii, K. J., Coban, C., Hemmi, H., Yamamoto, M., Terai, K., Matsuda, M., Inoue, J., Uematsu, S., et al. (2004) · Nature Immunology · doi:10.1038/ni1118 · Cited by 1,038 · see citing works
The role of inflammation in insulitis and β-cell loss in type 1 diabetes
Eizirik, D. L., Colli, M. L., & Ortis, F. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.21 · Cited by 1,011 · see citing works
Nejentsev, S., Walker, N., Riches, D., Egholm, M., & Todd, J. A. (2009) · Science · doi:10.1126/science.1167728 · Cited by 958 · see citing works
Self-citationVariations in DNA elucidate molecular networks that cause disease
Chen, Y., Zhu, J., Lum, P. Y., Yang, X., Pinto, S., MacNeil, D. J., Zhang, C., Lamb, J., Edwards, S., Sieberts, S. K., et al. (2008) · Nature · doi:10.1038/nature06757 · Cited by 887 · see citing works
Molecular networks as sensors and drivers of common human diseases
Schadt, E. E. (2009) · Nature · doi:10.1038/nature08454 · Cited by 806 · see citing works
Common Regulatory Variation Impacts Gene Expression in a Cell Type–Dependent Manner
Dimas, A. S., Deutsch, S., Stranger, B. E., Montgomery, S. B., Borel, C., Attar, H., Ingle, C., Beazley, C., Arcelus, M. G., Sekowska, M., et al. (2009) · Science · doi:10.1126/science.1174148 · Cited by 729 · see citing works
Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins
Holness, C. L. L., & Simmons, D. (1993) · Blood · doi:10.1182/blood.v81.6.1607.1607 · Cited by 716 · see citing works
Smyth, D. J., Cooper, J. D., Bailey, R., Field, S., Burren, O. S., Smink, L. J., Guja, C., Ionescu-Tirgoviste, C., Widmer, B., Dunger, D. B., et al. (2006) · Nature Genetics · doi:10.1038/ng1800 · Cited by 688 · see citing works
Self-citationTrans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factors
Yvert, G., Brem, R. B., Whittle, J., Akey, J. M., Foss, E. J., Smith, E. N., Mackelprang, R., & Kruglyak, L. (2003) · Nature Genetics · doi:10.1038/ng1222 · Cited by 629 · see citing works
Genetics and Beyond – The Transcriptome of Human Monocytes and Disease Susceptibility
Zeller, T., Wild, P. S., Szymczak, S., Rotival, M., Schillert, A., Castagné, R., Maouche, S., Germain, M., Lackner, K. J., Rossmann, H., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010693 · Cited by 584 · see citing works
Self-citationHübner, N., Wallace, C. A., Zimdahl, H., Petretto, E. G., Schulz, H., MacIver, F. H., Mueller, M., Hummel, O., Monti, J., Zı́dek, V., et al. (2005) · Nature Genetics · doi:10.1038/ng1522 · Cited by 512 · see citing works
Self-citationEBI2 mediates B cell segregation between the outer and centre follicle
Pereira, J. P., Kelly, L. M., Xu, Y., & Cyster, J. G. (2009) · Nature · doi:10.1038/nature08226 · Cited by 398 · see citing works
Self-citationGuidance of B Cells by the Orphan G Protein-Coupled Receptor EBI2 Shapes Humoral Immune Responses
Gatto, D., Paus, D., Basten, A., Mackay, C. R., & Brink, R. A. (2009) · Immunity · doi:10.1016/j.immuni.2009.06.016 · Cited by 302 · see citing works
Genetical Genomics: Spotlight on QTL Hotspots
Rainer Breitling, A., Li, Y., Tesson, B. M., Fu, J., Wu, C., Wiltshire, T., Gerrits, A., Bystrykh, L. V., de Haan, G., Su, A. I., et al. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000232 · Cited by 191 · see citing works
Self-citationSNP and haplotype mapping for genetic analysis in the rat
Saar, K., Heinig, M., Hummel, O., Lee, Y.-A., Patone, G., Schulz, H., Zimdahl, H., Hübner, N., Beck, A., Klages, S., et al. (2008) · Nature Genetics · doi:10.1038/ng.124 · Cited by 189 · see citing works
Self-citationGSEA-SNP: applying gene set enrichment analysis to SNP data from genome-wide association studies
Holden, M., Deng, S., Wojnowski, L., & Kulle, B. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn516 · Cited by 187 · see citing works
Interferon-α initiates type 1 diabetes in nonobese diabetic mice
Li, Q., Xu, B., Michie, S. A., Rubins, K., Schreriber, R. D., & McDevitt, H. O. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806439105 · Cited by 182 · see citing works
Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass
Petretto, E. G., Sarwar, R., Grieve, I. C., Han, L., Kumaran, M. K., Muckett, P. J., Mangion, J., Schroen, B. L. M., Benson, M. A., Punjabi, P. P., et al. (2008) · Nature Genetics · doi:10.1038/ng.134 · Cited by 164 · see citing works
Self-citationPASTAA: identifying transcription factors associated with sets of co-regulated genes
Roider, H. G., Manke, T., O'Keeffe, S., Vingron, M., & Haas, S. A. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btn627 · Cited by 154 · see citing works
Self-citationPlagnol, V., Smyth, D. J., Todd, J. A., & Clayton, D. G. (2009) · Biostatistics · doi:10.1093/biostatistics/kxn039 · Cited by 113 · see citing works
Self-citationNew Insights into the Genetic Control of Gene Expression using a Bayesian Multi-tissue Approach
Petretto, E. G., Bottolo, L., Langley, S. R., Heinig, M., McDermott‐Roe, C., Sarwar, R., Pravenec, M., Hübner, N., Aitman, T. J., Cook, S. A., et al. (2010) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000737 · Cited by 101 · see citing works
Self-citationThe genome sequence of the spontaneously hypertensive rat: Analysis and functional significancePreprint
Atanur, S. S., Birol, İ., Guryev, V., Hirst, M., Hummel, O., Morrissey, C., Behmoaras, J. V., Fernández, X. M., Johnson, M. D., McLaren, W. M., et al. (2010) · Genome Research · doi:10.1101/gr.103499.109 · Cited by 94 · see citing works
Self-citationCooper, J. D., Walker, N. M., Smyth, D. J., Downes, K., Healy, B. C., & Todd, J. A. (2009) · Genes and Immunity · doi:10.1038/gene.2009.97 · Cited by 60 · see citing works
Self-citationvon Herrath, M. (2009) · Nature · doi:10.1038/459518a · Cited by 59 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Multi-omics approaches to disease
Hasin, Y., Seldin, M., & Lusis, A. (2017) · Genome Biology · doi:10.1186/s13059-017-1215-1 · Cited by 2,953 · see citing works
Systematic identification of trans eQTLs as putative drivers of known disease associations
Westra, H.-J., Peters, M. J., Esko, T., Yaghootkar, H., Schurmann, C., Kettunen, J., Christiansen, M. W., Fairfax, B. P., Schramm, K., Powell, J. E., et al. (2013) · Nature Genetics · doi:10.1038/ng.2756 · Cited by 1,658 · see citing works
Self-citationThe role of regulatory variation in complex traits and disease
Albert, F. W., & Kruglyak, L. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3891 · Cited by 1,047 · see citing works
Bentham, J., Morris, D. L., Graham, D. S. C., Pinder, C. L., Tombleson, P., Behrens, T. W., Martin, J. J., Fairfax, B. P., Knight, J. C., Chen, L., et al. (2015) · Nature Genetics · doi:10.1038/ng.3434 · Cited by 990 · see citing works
DNA methylation and body-mass index: a genome-wide analysis
Dick, K. J., Nelson, C. P., Tsaprouni, L., Sandling, J. K., Aïssi, D., Wahl, S., Meduri, E., Morange, P.-E., Gagnon, F., Grallert, H., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(13)62674-4 · Cited by 778 · see citing works
Self-citationMapping cis- and trans-regulatory effects across multiple tissues in twins
The Multiple Tissue Human Expression Resource (MuTHER) Consortium, Grundberg, E., Small, K. S., Hedman, Å. K., Nica, A. C., Buil, A., Keildson, S., Bell, J. T., Yang, T.-P., Meduri, E., et al. (2012) · Nature Genetics · doi:10.1038/ng.2394 · Cited by 729 · see citing works
Önengüt-Gümüşcü, S., Chen, W., Burren, O. S., Cooper, N. J., Quinlan, A. R., Mychaleckyj, J. C., Farber, E., Bonnie, J. K., Szpak, M., Schofield, E. C., et al. (2015) · Nature Genetics · doi:10.1038/ng.3245 · Cited by 675 · see citing works
Self-citationSystems genetics approaches to understand complex traits
Civelek, M., & Lusis, A. J. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3575 · Cited by 621 · see citing works
IRF7: activation, regulation, modification and function
Ning, S., Pagano, J. S., & Barber, G. N. (2011) · Genes and Immunity · doi:10.1038/gene.2011.21 · Cited by 590 · see citing works
Oxysterols direct immune cell migration via EBI2
Hannedouche, S., Zhang, J., Yi, T., Shen, W., Nguyen, D. G., Pereira, J. P., Guerini, D., Baumgarten, B. U., Roggo, S. P., Wen, B. G., et al. (2011) · Nature · doi:10.1038/nature10280 · Cited by 489 · see citing works
Self-citation25-Hydroxycholesterols in innate and adaptive immunity
Cyster, J. G., Dang, E. V., Reboldi, A., & Yi, T. (2014) · Nature Reviews Immunology · doi:10.1038/nri3755 · Cited by 388 · see citing works
Self-citationVillard, E., Perret, C., Gary, F., Proust, C., Dilanian, G., Hengstenberg, C., Ruppert, V., Arbustini, E., Wichter, T., Germain, M., et al. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr105 · Cited by 341 · see citing works
Self-citationA Genome-Wide Meta-Analysis of Six Type 1 Diabetes Cohorts Identifies Multiple Associated Loci
Bradfield, J. P., Qu, H., Wang, K., Zhang, H., Abou‐Sleiman, P. M., Kim, C. E., Mentch, F. D., Qiu, H., Glessner, J., Thomas, K., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002293 · Cited by 338 · see citing works
Ferreira, R. C., Guo, H., Coulson, R., Smyth, D. J., Pękalski, M. Ł., Burren, O. S., Cutler, A. J., Doecke, J. D., Flint, S. M., McKinney, E. F., et al. (2014) · Diabetes · doi:10.2337/db13-1777 · Cited by 313 · see citing works
Self-citationFast and Rigorous Computation of Gene and Pathway Scores from SNP-Based Summary Statistics
Lamparter, D., Marbach, D., Rueedi, R., Kutalik, Z., & Bergmann, S. (2016) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004714 · Cited by 312 · see citing works
Viral infections in type 1 diabetes mellitus — why the β cells?
Op de Beeck, A., & Eizirik, D. L. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.30 · Cited by 291 · see citing works
Die Gutenberg Gesundheitsstudie
Wild, P. S., Zeller, T., Beutel, M. E., Blettner, M., Dugi, K. A., Lackner, K. J., Pfeiffer, N., Münzel, T. F., & Blankenberg, S. (2012) · Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz · doi:10.1007/s00103-012-1502-7 · Cited by 240 · see citing works
Self-citationUnderstanding type 1 diabetes through genetics: advances and prospects
Polychronakos, C., & Li, Q. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3069 · Cited by 226 · see citing works
Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome
Charchar, F. J., Bloomer, L. D. S., Barnes, T. A., Cowley, M. J., Nelson, C. P., Wang, Y., Denniff, M. J., Dębiec, R., Christofidou, P., Nankervis, S. A., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(11)61453-0 · Cited by 216 · see citing works
Self-citationMetagenomics and Personalized Medicine
Virgin, H. W., & Todd, J. A. (2011) · Cell · doi:10.1016/j.cell.2011.09.009 · Cited by 203 · see citing works
Self-citationKallionpää, H., Elo, L. L., Laajala, E., Mykkänen, J., Ricaño-Ponce, I., Vaarma, M., Laajala, T. D., Hyöty, H., Ilonen, J., Veijola, R., et al. (2014) · Diabetes · doi:10.2337/db13-1775 · Cited by 187 · see citing works
Genetics of trans-regulatory variation in gene expression
Albert, F. W., Bloom, J. S., Siegel, J. J., Day, L., & Kruglyak, L. (2018) · eLife · doi:10.7554/elife.35471 · Cited by 180 · see citing works
Johnson, M. R., Behmoaras, J. V., Bottolo, L., Krishnan, M. L., Pernhorst, K., Santoscoy, P. L. M., Rossetti, T., Speed, D., Srivastava, P. K., Chadeau‐Hyam, M., et al. (2015) · Nature Communications · doi:10.1038/ncomms7031 · Cited by 174 · see citing works
Self-citationFrom genome to function by studying eQTLs
Westra, H.-J., & Franke, L. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.04.024 · Cited by 166 · see citing works
Atanur, S. S., Diaz, A. I. G., Maratou, K., Sarkis, A. B., Rotival, M., Gamé, L., Tschannen, M., Kaisaki, P. J., Otto, G., Ma, M. C. J., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.040 · Cited by 158 · see citing works
Self-citationEndonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function
McDermott‐Roe, C., Ye, J., Ahmed, R., Sun, X.-M., Serafin, A. M., Ware, J. S., Bottolo, L., Muckett, P. J., Cañas, X., Zhang, J., et al. (2011) · Nature · doi:10.1038/nature10490 · Cited by 157 · see citing works
Self-citationType 1 Diabetes Is Associated With Enterovirus Infection in Gut Mucosa
Oikarinen, M., Tauriainen, S., Oikarinen, S., Honkanen, T., Collin, P., Rantala, I. S., Mäki, M., Kaukinen, K., & Hyöty, H. (2012) · Diabetes · doi:10.2337/db11-1157 · Cited by 151 · see citing works
Seven newly identified loci for autoimmune thyroid disease
Cooper, J. D., Simmonds, M. J., Walker, N. M., Burren, O. S., Brand, O. J., Guo, H., Wallace, C., Stevens, H. E., Coleman, G., Franklyn, J. A., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds357 · Cited by 149 · see citing works
Self-citationmiR-451 Regulates Dendritic Cell Cytokine Responses to Influenza Infection
Rosenberger, C. M., Podyminogin, R. L., Navarro, G., Zhao, G., Askovich, P. S., Weiss, M. J., & Aderem, A. A. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1201437 · Cited by 142 · see citing works
Candidate genes for type 1 diabetes modulate pancreatic islet inflammation and β ‐cell apoptosis
Santín, I., & Eizirik, D. L. (2013) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12162 · Cited by 140 · see citing works
Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue
Shi, J., Marconett, C. N., Duan, J., Hyland, P. L., Li, P., Wang, Z., Wheeler, W., Zhou, B., Campan, M., Lee, D. S., et al. (2014) · Nature Communications · doi:10.1038/ncomms4365 · Cited by 137 · see citing works
Rotival, M., Zeller, T., Wild, P. S., Maouche, S., Szymczak, S., Schillert, A., Castagné, R., Deiseroth, A., Proust, C., Brocheton, J., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002367 · Cited by 137 · see citing works
Self-citationGenome–virome interactions: examining the role of common viral infections in complex disease
Foxman, E. F., & Iwasaki, A. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2541 · Cited by 136 · see citing works
IRF7: role and regulation in immunity and autoimmunity
Ma, W., Huang, G., Wang, Z., Wang, L., & Gao, Q. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1236923 · Cited by 130 · see citing works
GWAS in autoimmune thyroid disease: redefining our understanding of pathogenesis
Simmonds, M. J. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.56 · Cited by 130 · see citing works
Low, T. Y., van Heesch, S., van den Toorn, H., Giansanti, P., Cristobal, A., Toonen, P. W., Schäfer, S., Hübner, N., van Breukelen, B., Mohammed, S., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.10.041 · Cited by 125 · see citing works
Kelly, L. M., Pereira, J. P., Yi, T., Xu, Y., & Cyster, J. G. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1101262 · Cited by 125 · see citing works
Self-citationHuang, J., Sabater‐Lleal, M., Asselbergs, F. W., Trégouët, D., Shin, S., Ding, J., Baumert, J. J., Oudot‐Mellakh, T., Folkersen, L., Johnson, A. D., et al. (2012) · Blood · doi:10.1182/blood-2012-06-436188 · Cited by 122 · see citing works
Self-citationMolecular Mechanisms in Autoimmune Type 1 Diabetes: a Critical Review
Xie, Z., Chang, C., & Zhou, Z. (2014) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-014-8422-2 · Cited by 121 · see citing works
Defining the Transcriptional and Cellular Landscape of Type 1 Diabetes in the NOD Mouse
Carrero, J. A., Calderón, B., Towfic, F., Artyomov, M. N., & Unanue, E. R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059701 · Cited by 113 · see citing works
Davison, L. J., Wallace, C., Cooper, J. D., Cope, N. F., Wilson, N. K., Smyth, D. J., Howson, J. M. M., Saleh, N. M., Aljeffery, A., Angus, K. L., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr468 · Cited by 107 · see citing works
Self-citationZhang, P., He, Q., Chen, D., Liu, W., Wang, L., Zhang, C., Ma, D., Li, W., Liu, B., & Liu, F. (2015) · Cell Research · doi:10.1038/cr.2015.109 · Cited by 107 · see citing works
Quantitative Interaction Proteomics of Neurodegenerative Disease Proteins
Hosp, F., Voßfeldt, H., Heinig, M., Vasiljević, D., Arumughan, A., Wyler, E., Landthaler, M., Hübner, N., Wanker, E. E., Lannfelt, L., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.030 · Cited by 101 · see citing works
Self-citationStatistical colocalization of monocyte gene expression and genetic risk variants for type 1 diabetes
Wallace, C., Rotival, M., Cooper, J. D., Rice, C. M., Yang, J. H. M., McNeill, M., Smyth, D. J., Niblett, D., Cambien, F., Tiret, L., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds098 · Cited by 101 · see citing works
Self-citationGatto, D., Wood, K., & Brink, R. A. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1101542 · Cited by 101 · see citing works
Network representations of immune system complexity
Subramanian, N., Torabi‐Parizi, P., Gottschalk, R. A., Germain, R. N., & Dutta, B. (2015) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1288 · Cited by 100 · see citing works
A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target
Srivastava, P. K., van Eyll, J. M., Godard, P., Mazzuferi, M., Delahaye‐Duriez, A., Steenwinckel, J. V., Gressèns, P., Danis, B., Vandenplas, C., Foerch, P., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06008-4 · Cited by 100 · see citing works
Self-citationInflammatory Cell Migration in Rheumatoid Arthritis: A Comprehensive Review
Nevius, E., Gomes, A. C., & Pereira, J. P. (2015) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-015-8520-9 · Cited by 98 · see citing works
Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes
Szpirer, C. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-020-00673-8 · Cited by 93 · see citing works
Kirchhof, P. F., Medicine, E. C. R. A. E. A. W. S. O. P., Sipido, K. R., Medicine, E. C. R. A. E. A. W. S. O. P., Cowie, M., Medicine, E. C. R. A. E. A. W. S. O. P., Eschenhagen, T., Medicine, E. C. R. A. E. A. W. S. O. P., Fox, K. A. A., Medicine, E. C. R. A. E. A. W. S. O. P., et al. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu312 · Cited by 91 · see citing works
Self-citationClinical features and outcomes of 98 children and adults with dense deposit disease
Lu, D.-F., Moon, M., Lanning, L. D., McCarthy, A. M., & Smith, R. J. (2011) · Pediatric Nephrology · doi:10.1007/s00467-011-2059-7 · Cited by 91 · see citing works
From genetics of inflammatory bowel disease towards mechanistic insights
Graham, D. B., & Xavier, R. J. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.04.001 · Cited by 86 · see citing works
B cell localization: regulation by EBI2 and its oxysterol ligand
Gatto, D., & Brink, R. A. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.01.007 · Cited by 86 · see citing works
The Role of Epigenetics in Type 1 Diabetes
Jerram, S. T., Dang, M. N., & Leslie, R. D. (2017) · Current Diabetes Reports · doi:10.1007/s11892-017-0916-x · Cited by 85 · see citing works
Liquet, B., Bottolo, L., Campanella, G., Richardson, S. T., & Chadeau‐Hyam, M. (2016) · Journal of Statistical Software · doi:10.18637/jss.v069.i02 · Cited by 84 · see citing works
Self-citationStem-cell based organ-on-a-chip models for diabetes research
Rogal, J., Zbinden, A., Schenke‐Layland, K., & Loskill, P. (2018) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.10.010 · Cited by 83 · see citing works
Schurmann, C., Heim, K., Schillert, A., Blankenberg, S., Carstensen, M., Dörr, M., Endlich, K., Felix, S. B., Gieger, C., Grallert, H., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050938 · Cited by 80 · see citing works
Self-citationSantín, I., Moore, F., Grieco, F. A., Marchetti, P., Brancolini, C., & Eizirik, D. L. (2012) · Cell Death and Disease · doi:10.1038/cddis.2012.158 · Cited by 80 · see citing works
Genomewide Association Studies in Cardiovascular Disease—An Update 2011
Zeller, T., Blankenberg, S., & Diemert, P. (2011) · Clinical Chemistry · doi:10.1373/clinchem.2011.170431 · Cited by 78 · see citing works
Self-citationPoitou, C., Perret, C., Mathieu, F., Trương, V., Blum, Y., Durand, H., Alili, R., Chelghoum, N., Pelloux, V., Aron‐Wisnewsky, J., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125718 · Cited by 77 · see citing works
Self-citationLeukocyte Chemoattractant Receptors in Human Disease Pathogenesis
Zabel, B. A., Rott, A., & Butcher, E. C. (2014) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012513-104640 · Cited by 76 · see citing works
Regulation of Fn14 Receptor and NF-κB Underlies Inflammation in Meniere’s Disease
Frejo, L., Requena, T., Okawa, S., Gallego‐Martinez, A., Martínez‐Bueno, M., Arán, I., Caletrío, Á. B., Benitez-Rosario, J., Espinosa-Sánchez, J. M., Fraile, J. J., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01739 · Cited by 76 · see citing works
Bloomer, L. D. S., Nelson, C. P., Eales, J., Denniff, M., Christofidou, P., Debiec, R., Moore, J., Consortium, C., Zukowska-Szczechowska, E., Goodall, A. H., et al. (2013) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.113.301608 · Cited by 75 · see citing works
Self-citationWWP2 regulates pathological cardiac fibrosis by modulating SMAD2 signaling
Chen, H., Moreno‐Moral, A., Pesce, F., Devapragash, N., Mancini, M., Heng, E. L., Rotival, M., Srivastava, P. K., Harmston, N., Shkura, K., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11551-9 · Cited by 75 · see citing works
Self-citationThe future of model organisms in human disease research
Aitman, T. J., Boone, C. M., Churchill, G. A., Hengartner, M. O., Mackay, T. F. C., & Stemple, D. L. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3047 · Cited by 75 · see citing works
Self-citationMid-Gestational Gene Expression Profile in Placenta and Link to Pregnancy Complications
Uusküla-Reimand, L., Männik, J., Rull, K., Minajeva, A., Kõks, S., Vaas, P., Teesalu, P., Reimand, J., & Laan, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049248 · Cited by 74 · see citing works
Strategies to discover regulatory circuits of the mammalian immune system
Amit, I., Regev, A., & Hacohen, N. (2011) · Nature reviews. Immunology · doi:10.1038/nri3109 · Cited by 73 · see citing works
Genetic influences on brain gene expression in rats selected for tameness and aggression
Heyne, H. O., Lautenschläger, S., Nelson, R., Besnier, F., Rotival, M., Cagan, A., Kozhemyakina, R., Plyusnina, I. Z., Trut, L., Carlborg, Ö., et al. (2014) · Genetics · doi:10.1534/genetics.114.168948 · Cited by 72 · see citing works
Self-citationHeinig, M., Adriaens, M. E., Schäfer, S., van Deutekom, H. W. M., Lodder, E. M., Ware, J. S., Schneider-Lunitz, V., Felkin, L. E., Creemers, E. E., Meder, B., et al. (2017) · Genome biology · doi:10.1186/s13059-017-1286-z · Cited by 72 · see citing works
Self-citationThe Genetic Architecture of Type 1 Diabetes
Jerram, S. T., & Leslie, R. D. (2017) · Genes · doi:10.3390/genes8080209 · Cited by 72 · see citing works
Bayesian Detection of Expression Quantitative Trait Loci Hot Spots
Bottolo, L., Petretto, E. G., Blankenberg, S., Cambien, F., Cook, S. A., Tiret, L., & Richardson, S. T. (2011) · Genetics · doi:10.1534/genetics.111.131425 · Cited by 71 · see citing works
Self-citationAging-related defects in macrophage function are driven by MYC and USF1 transcriptional programs
Moss, C. E., Johnston, S. A., Kimble, J. V., Clements, M., Codd, V., Hamby, S. E., Goodall, A. H., Deshmukh, S., Sudbery, I. M., Coca, D., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114073 · Cited by 71 · see citing works
Self-citationOxysterols in intestinal immunity and inflammation
Willinger, T. (2018) · Journal of Internal Medicine · doi:10.1111/joim.12855 · Cited by 71 · see citing works
Ten years of genetics and genomics: what have we achieved and where are we heading?
Heard, É., Tishkoff, S. A., Todd, J. A., Vidal, M., Wagner, G. P., Wang, J., Weigel, D., & Young, R. A. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2878 · Cited by 69 · see citing works
Self-citationSenatus, L. M., López‐Díez, R., Egaña-Gorroño, L., Liu, J., Hu, J., Daffu, G. K., Li, Q., Rahman, K., Vengrenyuk, Y., Barrett, T. J., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.137289 · Cited by 68 · see citing works
Nevius, E., Pinho, F. O., Dhodapkar, M. M., Jin, H., Nadrah, K., Horowitz, M. C., Kikuta, J., Ishii, M., & Pereira, J. P. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20150088 · Cited by 67 · see citing works
Xiao, X., Moreno-Moral, A., Rotival, M., Bottolo, L., & Petretto, E. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004006 · Cited by 63 · see citing works
Self-citationGessier, F., Preuß, I., Yin, H., ROSENKILDE, M. M., Laurent, S., Endres, R., Chen, Y. A., Marsilje, T. H., Seuwen, K., Nguyen, D. G., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm4019355 · Cited by 63 · see citing works
Honke, N., Shaabani, N., Zhang, D., Iliakis, G. E., Xu, H. C., Häussinger, D., Recher, M., Löhning, M., Lang, P. A., & Lang, K. S. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003650 · Cited by 63 · see citing works
Developing a vaccine for type 1 diabetes by targeting coxsackievirus B
Hyöty, H., Leon, F., & Knip, M. (2018) · Expert Review of Vaccines · doi:10.1080/14760584.2018.1548281 · Cited by 63 · see citing works
Natural variation of histone modification and its impact on gene expression in the rat genomePreprint
Rintisch, C., Heinig, M., Bauerfeind, A., Schäfer, S., Mieth, C., Patone, G., Hummel, O., Chen, W., Cook, S. A., Cuppen, E. P. J. G., et al. (2014) · Genome Research · doi:10.1101/gr.169029.113 · Cited by 58 · see citing works
Self-citationGenome-Wide Haplotype Analysis of Cis Expression Quantitative Trait Loci in Monocytes
Garnier, S., Trương, V., Brocheton, J., Zeller, T., Rovital, M., Wild, P. S., Ziegler, A., Münzel, T. F., Tiret, L., Blankenberg, S., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003240 · Cited by 56 · see citing works
Self-citationInfection as a cause of type 1 diabetes?
Christen, U., Bender, C., & von Herrath, M. G. (2012) · Current Opinion in Rheumatology · doi:10.1097/bor.0b013e3283533719 · Cited by 56 · see citing works
Recent Progress in the Genetics of Spontaneously Hypertensive Rats
Pravenec, M., Křen, V., Landa, V., Mlejnek, P., Musilová, A., Šilhavý, J., Šimáková, M., & Zı́dek, V. (2014) · Physiological Research · doi:10.33549/physiolres.932622 · Cited by 56 · see citing works
Self-citationTherapeutic Targeting of IRFs: Pathway-Dependence or Structure-Based?
Thompson, C. D., Matta, B., & Barnes, B. J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02622 · Cited by 56 · see citing works
Effects of Oxysterols on Immune Cells and Related Diseases
de Freitas, F. A., Levy, D., Reichert, C. O., Cunha‐Neto, E., Kalil, J. E., & Bydlowski, S. P. (2022) · Cells · doi:10.3390/cells11081251 · Cited by 55 · see citing works
Zhang, X., Johnson, A. D., Hendricks, A. E., Hwang, S., Tanrıverdi, K., Ganesh, S. K., Smith, N. L., Peyser, P. A., Freedman, J. E., & O’Donnell, C. J. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt461 · Cited by 55 · see citing works
The Adipokine-Cardiovascular-Lifestyle Network
Mechanick, J. I., Zhao, S., & Garvey, W. T. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.06.072 · Cited by 55 · see citing works
Interferon regulatory factor signaling in autoimmune disease
Matta, B., Song, S., Li, D., & Barnes, B. J. (2017) · Cytokine · doi:10.1016/j.cyto.2017.02.006 · Cited by 55 · see citing works
Type 1 diabetes and gut microbiota: Friend or foe?
Hu, C., Wong, F. S., & Li, W. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.02.006 · Cited by 53 · see citing works
Sjoelund, V. H., Smelkinson, M. G., & Nita‐Lazar, A. (2014) · Journal of Proteome Research · doi:10.1021/pr5002466 · Cited by 52 · see citing works
The problems and promises of research into human immunology and autoimmune disease
Roep, B. O., Buckner, J. H., Sawcer, S. J., Toes, R. E. M., & Zipp, F. (2012) · Nature Medicine · doi:10.1038/nm.2626 · Cited by 51 · see citing works
Duc, D., Vigne, S., & Pot, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20184522 · Cited by 51 · see citing works
Asymptotically independent U-statistics in high-dimensional testing
He, Y., Xu, G., Wu, C., & Pan, W. (2021) · The Annals of Statistics · doi:10.1214/20-aos1951 · Cited by 51 · see citing works
Mirza, N., Appleton, R. E., Burn, S. C., Carr, D. F., Crooks, D. A., du Plessis, D., Duncan, R., Farah, J. O., Josan, V., Miyajima, F., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv163 · Cited by 49 · see citing works
Frascoli, M., Ferraj, E., Miu, B., Malin, J., Spidale, N. A., Cowan, J. E., Shissler, S. C., Brink, R. A., Xu, Y., Cyster, J. G., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.01.025 · Cited by 48 · see citing works
Self-citationThe stroke-prone spontaneously hypertensive rat: still a useful model for post-GWAS genetic studies?
Nabika, T., Ohara, H., Kato, N., & Isomura, M. (2012) · Hypertension Research · doi:10.1038/hr.2012.30 · Cited by 48 · see citing works
Anagandula, M. K., Richardson, S. J., Oberste, M. S., Sioofy‐Khojine, A., Hyöty, H., Morgan, N. G., Korsgren, O., & Frisk, G. (2013) · Journal of Medical Virology · doi:10.1002/jmv.23835 · Cited by 47 · see citing works
Systematic Evaluation of Genes and Genetic Variants Associated with Type 1 Diabetes Susceptibility
Ram, R., Mehta, M., Nguyen, Q. T., Larma, I., Boehm, B. O., Pociot, F., CONCANNON, P. J., & Morahan, G. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502056 · Cited by 47 · see citing works
Oxysterol‐EBI2 signaling in immune regulation and viral infection
Daugvilaite, V., Arfelt, K. N., Benned‐Jensen, T., Sailer, A. W., & ROSENKILDE, M. M. (2014) · European Journal of Immunology · doi:10.1002/eji.201444493 · Cited by 46 · see citing works
- Authors
- Cardiogenics Consortium, Heinig, M., Petretto, E., Wallace, C., Bottolo, L., Rotival, M., Lu, H., Li, Y., Sarwar, R., Langley, S. R., Bauerfeind, A., Hummel, O., Lee, Y.-A., Paskas, S., Rintisch, C., Saar, K., Cooper, J., Buchan, R., Gray, E. E., Cyster, J. G., Erdmann, J., Hengstenberg, C., Maouche, S., Ouwehand, W. H., Rice, C. M., Samani, N. J., Schunkert, H., Goodall, A. H., Schulz, H., Roider, H. G., Vingron, M., Blankenberg, S., Münzel, T., Zeller, T., Szymczak, S., Ziegler, A., Tiret, L., Smyth, D. J., Pravenec, M., Aitman, T. J., Cambien, F., Clayton, D., Todd, J. A., Hubner, N., & Cook, S. A.
- Affiliations
- Max Delbrück Center (DE)
- Hammersmith Hospital (GB)
- University of Cambridge (GB)
- Inserm (FR)
- Howard Hughes Medical Institute (US)
- University of Lübeck (DE)
- University of Regensburg (DE)
- National Health Service (GB)
- Wellcome Sanger Institute (GB)
- University of Leicester (GB)
- Max Planck Institute for Molecular Genetics (DE)
- Johannes Gutenberg University Mainz (DE)
- University Hospital Schleswig-Holstein (DE)
- Czech Academy of Sciences (CZ)
- Corresponding author
- Cook, Stuart A.
- ORCID
- Heinig, Matthias
- Petretto, Enrico
- Wallace, Chris
- Bottolo, Leonardo
- Rotival, Maxime
- Sarwar, Rizwan
- Langley, Sarah R.
- Hummel, Oliver
- Lee, Young-Ae
- Saar, Kathrin
- Cooper, Jason
- Buchan, Rachel
- Gray, Elizabeth E.
- Cyster, Jason G.
- Erdmann, Jeanette
- Maouche, Seraya
- Ouwehand, Willem H.
- Samani, Nilesh J.
- Schunkert, Heribert
- Goodall, Alison H.
- Schulz, Herbert
- Roider, Helge G.
- Vingron, Martin
- Blankenberg, Stefan
- Münzel, Thomas
- Zeller, Tanja
- Szymczak, Silke
- Ziegler, Andreas
- Smyth, Deborah J.
- Pravenec, Michal
- Aitman, Timothy J.
- Clayton, David
- Todd, John A.
- Cook, Stuart A.
- Venue
- Nature
- Published
- 2010-09
- Volume
- 467
- Issue
- 7314
- Pages
- 460-464
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3657719
- OpenAlex
- W2166903146
- Cited by
- 283
- References
- 30
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 9 · 2023: 8 · 2022: 9 · 2021: 23 · 2020: 8 · 2019: 16 · 2018: 13 · 2017: 20 · 2016: 20 · 2015: 22 · 2014: 27 · 2013: 26 · 2012: 38
- FWCI
- 18.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- National University of Singapore (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- ASEP (submittedVersion, public-domain)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Site cant be reached (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Juvenile Diabetes Research Foundation International
- Wellcome Trust (FP7/2007–2013, 061858, 089989, 076113)
- University Hospitals of Leicester NHS Trust
- National Institute for Health and Care Research (FP7/2007–2013, NF-SI-0508-10275)
- British Heart Foundation (P301/10/0290)
- Research Councils UK
- Imperial College London
- European Commission (2007–2013, LSHG-CT-2005-019015, FP7 2007-2013, LSHM-CT 2006–037593, FP7/2007, 241504)
- Fondation Leducq
- Grantová Agentura České Republiky (1M6837805002)
- Medical Research Council
- National Institute of Diabetes and Digestive and Kidney Diseases
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- type 1 diabetes, IRF7, EBI2, GPR183, macrophages, Epstein-Barr virus, monocytes, gene co-expression network, autoimmune disease susceptibility, systems genetics
- MeSH terms
- Animals, Base Sequence, Chromosomes, Human, Pair 13, Diabetes Mellitus, Type 1, Humans, Immunity, Innate, Inflammation, Macrophages, Organ Specificity, Viruses, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Chromosomes, Mammalian, Quantitative Trait Loci, Receptors, G-Protein-Coupled, Interferon Regulatory Factor-7, Rats, Gene Regulatory Networks, Genome-Wide Association Study, Genetic Loci
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
