A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk

Nature

Volumn 467, Issue 7314, 2010, Pages 460-464

  Heinig, Matthias ^a,b   Petretto, Enrico ^c,d   Wallace, Chris ^e   Bottolo, Leonardo ^c,d   Rotival, Maxime ^f   Lu, Han ^c   Li, Yoyo ^c   Sarwar, Rizwan ^c   Langley, Sarah R ^c   Bauerfeind, Anja ^a   Hummel, Oliver ^a   Lee, Young Ae ^a,g   Paskas, Svetlana ^a   Rintisch, Carola ^a   Saar, Kathrin ^a   Cooper, Jason ^e   Buchan, Rachel ^c   Gray, Elizabeth E ^h   Cyster, Jason G ^h   Jeanette Erdmann, ⁱ   Hengstenberg, Christian ^j   Maouche, Seraya ^f   Ouwehand, Willem H ^k,l   Rice, Catherine M ^l   Samani, Nilesh J ^m   Schunkert, Heribert ⁱ   Goodall, Alison H ^m   Schulz, Herbert ^a   Roider, Helge G ^b   Vingron, Martin ^b   Blankenberg, Stefan ⁿ   Münzel, Thomas ⁿ   Zeller, Tanja ⁿ   Szymczak, Silke ^o   Ziegler, Andreas ^o   Tiret, Laurence ^f   Smyth, Deborah J ^e   Pravenec, Michal ^p   Aitman, Timothy J ^c   Cambien, Francois ^f   Clayton, David ^e   Todd, John A ^e   Hubner, Norbert ^a,g   Cook, Stuart A ^c,q   Braund, Peter ^m   Gracey, Jay ^m   Krishnan, Unni ^m   Moore, Jasbir S ^m   Nelson, Chris P ^m   Pollard, Helen ^m   Attwood, Tony ^k   Crisp Hihn, Abi ^k   Foad, Nicola ^k   Jolley, Jennifer ^k   Lloyd Jones, Heather ^k   Muir, David ^k   Murray, Elizabeth ^k   O'Leary, Karen ^k   Rankin, Angela ^k   Sambrook, Jennifer ^k   Godfroy, Tiphaine ^r   Brocheton, Jessy ^r   Proust, Carole ^r   Schmitz, Gerd ^s   Heimerl, Susanne ^j   Lugauer, Ingrid ^j   Belz, Stephanie ⁱ   Gulde, Stefanie ⁱ   Linsel Nitschke, Patrick ⁱ   Sager, Hendrik ⁱ   Schroeder, Laura ⁱ   Lundmark, Per ^t   Syvannen, Ann Christine ^t   Neudert, Jessica ^u   Scholz, Michael ^u   Deloukas, Panos ^l   Gray, Emma ^l   Gwilliams, Rhian ^l   Niblett, David ^l   more..

^a MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

^b MAX PLANCK INSTITUTE FOR MOLECULAR GENETICS   (Germany)

^c HAMMERSMITH HOSPITAL   (United Kingdom)

^d IMPERIAL COLLEGE LONDON   (United Kingdom)

^e UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^f INSERM   (France)

^g CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^h UNIVERSITY OF CALIFORNIA   (United States)

ⁱ UNIVERSITY OF LÜBECK   (Germany)

^j UNIVERSITY HOSPITAL REGENSBURG   (Germany)

^k UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^l WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^m UNIVERSITY OF LEICESTER   (United Kingdom)

ⁿ JOHANNES GUTENBERG UNIVERSITY   (Germany)

^o UNIVERSITY HOSPITAL SCHLESWIG HOLSTEIN   (Germany)

^p INSTITUTE OF PHYSIOLOGY   (Czech Republic)

^q NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

^r SORBONNE UNIVERSITÉ   (France)

^s UNIVERSITY OF REGENSBURG   (Germany)

^t UPPSALA UNIVERSITY   (Sweden)

^u TRIUM ANALYSIS ONLINE GMBH   (Germany)

more..

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; INTERFERON REGULATORY FACTOR 7; G PROTEIN COUPLED RECEPTOR; GPR183 PROTEIN, RAT;

BIOMARKER; DIABETES; ETIOLOGY; GENETIC ANALYSIS; GENOME; HEALTH RISK; IMMUNE RESPONSE; POLYMORPHISM; RODENT; VIRUS;

ANIMAL TISSUE; ARTICLE; B LYMPHOCYTE; CHROMOSOME 13Q; CHROMOSOME 15Q; EPSTEIN BARR VIRUS INDUCED GENE 2; GENE; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE LOCUS; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; INSULIN DEPENDENT DIABETES MELLITUS; LYMPHOCYTE MIGRATION; MACROPHAGE; MONOCYTE; NONHUMAN; PRIORITY JOURNAL; RAT; RISK ASSESSMENT; SINGLE NUCLEOTIDE POLYMORPHISM; ANIMAL; ANTIBODY SPECIFICITY; CHROMOSOME; CHROMOSOME 13; GENE REGULATORY NETWORK; GENETIC ASSOCIATION; GENETIC PREDISPOSITION; GENETICS; HUMAN; IMMUNOLOGY; INFLAMMATION; INNATE IMMUNITY; METABOLISM; NUCLEOTIDE SEQUENCE; QUANTITATIVE TRAIT LOCUS; VIRUS;

ANIMALS; BASE SEQUENCE; CHROMOSOMES, HUMAN, PAIR 13; CHROMOSOMES, MAMMALIAN; DIABETES MELLITUS, TYPE 1; GENE REGULATORY NETWORKS; GENETIC LOCI; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; IMMUNITY, INNATE; INFLAMMATION; INTERFERON REGULATORY FACTOR-7; MACROPHAGES; ORGAN SPECIFICITY; POLYMORPHISM, SINGLE NUCLEOTIDE; QUANTITATIVE TRAIT LOCI; RATS; RECEPTORS, G-PROTEIN-COUPLED; VIRUSES;

HUMAN HERPESVIRUS 4; RATTUS;

BAYESIAN NETWORKS; COMPLEX NETWORKS; MONTE CARLO METHODS; ORDINARY DIFFERENTIAL EQUATIONS; PARAMETER ESTIMATION; PROBABILITY DISTRIBUTIONS; SCATTERING PARAMETERS;

BAYES FACTOR; MARGINAL LIKELIHOOD; MODEL-BASED OPC; MULTI-COMPARTMENT MODELS; PARAMETER SPACES; POSTERIOR DISTRIBUTIONS; POWER; S -PARAMETERS; TRANS ACTINGS; TYPE 1 DIABETES;

REACTION RATES;

EID: 77957126059     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature09386     Document Type: Article

References (29)

1. Hubner, N. et al. Integrated transcriptional profiling and linkage analysis for identification of genes underlying disease. Nature Genet. 37, 243-253 (2005).
2. Petretto, E.etal. Integrated genomicapproaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass. Nature Genet. 40, 546-552 (2008).
3. Honda, K. et al. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature 434, 772-777 (2005).
4. Pereira, J. P., Kelly, L. M., Xu, Y. & Cyster, J. G. EBI2 mediates B cell segregation between the outer and centre follicle. Nature 460, 1122-1126 (2009).
5. Gatto, D., Paus, D., Basten, A., Mackay, C. R. & Brink, R. Guidance of B cells by the orphan G protein-coupled receptor EBI2 shapes humoral immune responses. Immunity 31, 259-269 (2009).
6. Altshuler, D., Daly,M.J.& Lander,E.S. Genetic mappinginhuman disease. Science 322, 881-888 (2008).
7. Schadt, E. E. Molecular networks as sensors and drivers of common human diseases. Nature 461, 218-223 (2009).
8. Chen, Y. et al. Variations in DNA elucidate molecular networks that cause disease. Nature 452, 429-435 (2008).
9. Dimas, A. S. et al. Common regulatory variation impacts gene expression in a cell type-dependent manner. Science 325, 1246-1250 (2009).
10. Brem, R. B., Yvert, G., Clinton, R.& Kruglyak, L.Genetic dissection oftranscriptional regulation in budding yeast. Science 296, 752-755 (2002)
11. Yvert, G. et al. Trans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factors. Nature Genet. 35, 57-64 (2003).
12. Roider, H. G., Manke, T., O'Keeffe, S., Vingron, M. & Haas, S. A. PASTAA: identifying transcription factors associated with setsof co-regulated genes. Bioinformatics 25, 435-442 (2009).
13. Petretto, E. et al. New insights into the genetic control of gene expression using a Bayesian multi-tissue approach. PLoS Comput. Biol. 6, e1000737 (2010).
14. Breitling, R. et al. Genetical genomics: spotlight on QTL hotspots. PLoS Genet. 4, e1000232 (2008).
15. Nathan, C. & Ding, A. Nonresolving inflammation. Cell 140, 871-882 (2010).
16. Eizirik,D. L., Colli,M. L. &Ortis,F.The roleof inflammationin insulitis and b-cell loss in type 1 diabetes. Nature Rev. Endocrinol. 5, 219-226 (2009).
17. Holness,C.L.& Simmons,D. L. Molecular cloning ofCD68, a human macrophage marker related to lysosomal glycoproteins. Blood 81, 1607-1613 (1993).
18. Saar, K. et al. SNP and haplotype mapping for genetic analysis in the rat. Nature Genet. 40, 560-566 (2008).
19. Atanur, S. S. et al. The genome sequence of the spontaneously hypertensive rat: analysis and functional significance. Genome Res. 20, 791-803 (2010).
20. Zeller, T. et al. Genetics and beyond-the transcriptome of human monocytes and disease susceptibility. PLoS ONE 5, e10693 (2010).
21. Plagnol, V., Smyth, D. J., Todd, J. A. & Clayton, D. G. Statistical independence of the colocalized association signals for type1diabetes and RPS26 gene expression on chromosome 12q13. Biostatistics 10, 327-334 (2009).
22. Von Herrath, M. Diabetes:a virus-gene collaboration.Nature 459, 518-519 (2009).
23. Nejentsev, S., Walker, N., Riches, D., Egholm, M. & Todd, J. A. Rare variants ofIFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes. Science 324, 387-389 (2009).
24. Smyth, D. J. et al. A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region. Nature Genet. 38, 617-619 (2006).
25. Barrett, J. C. etal. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nature Genet. 41, 703-707 (2009).
26. Li, Q. et al. Interferon-a initiates type 1 diabetes in nonobese diabetic mice. Proc. Natl Acad. Sci. USA 105, 12439-12444 (2008).
27. Cooper, J. D.etal. Follow-upof 1715 SNPs from the Wellcome Trust Case Control Consortium genome-wide association study in type I diabetes families. Genes Immun. 10 (suppl. 1), S85-S94 (2009).
28. Kawai, T. et al. Interferon-a induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nature Immunol. 5, 1061-1068 (2004).
29. The. Wellcome Trust CaseControl Consortium. Genome-wide association study of 14,000 casesof seven common diseases and 3,000 shared controls. Nature 447, 661-678 (2007).