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

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A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk. / Heinig, Matthias; Petretto, Enrico; Wallace, Chris; Bottolo, Leonardo; Rotival, Maxime; Lu, Han; Li, Yoyo; Sarwar, Rizwan; Langley, Sarah R; Bauerfeind, Anja; Hummel, Oliver; Lee, Young-Ae; Paskas, Svetlana; Rintisch, Carola; Saar, Kathrin; Cooper, Jason; Buchan, Rachel; Gray, Elizabeth E; Cyster, Jason G; Erdmann, Jeanette; Hengstenberg, Christian; Maouche, Seraya; Ouwehand, Willem H; Rice, Catherine M; 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; Tiret, Laurence; Smyth, Deborah J; Pravenec, Michal; Aitman, Timothy J; Cambien, Francois; Clayton, David; Todd, John A; Hubner, Norbert; Cook, Stuart A; CardioGenics Consortium.

In: NATURE, Vol. 467, No. 7314, 23.09.2010, p. 460-464.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Heinig, M, Petretto, E, Wallace, C, Bottolo, L, Rotival, M, Lu, H, Li, Y, Sarwar, R, Langley, SR, Bauerfeind, A, Hummel, O, Lee, Y-A, Paskas, S, Rintisch, C, Saar, K, Cooper, J, Buchan, R, Gray, EE, Cyster, JG, Erdmann, J, Hengstenberg, C, Maouche, S, Ouwehand, WH, Rice, CM, Samani, NJ, Schunkert, H, Goodall, AH, Schulz, H, Roider, HG, Vingron, M, Blankenberg, S, Münzel, T, Zeller, T, Szymczak, S, Ziegler, A, Tiret, L, Smyth, DJ, Pravenec, M, Aitman, TJ, Cambien, F, Clayton, D, Todd, JA, Hubner, N, Cook, SA & CardioGenics Consortium 2010, 'A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk', NATURE, vol. 467, no. 7314, pp. 460-464. https://doi.org/10.1038/nature09386

APA

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., ... CardioGenics Consortium (2010). A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk. NATURE, 467(7314), 460-464. https://doi.org/10.1038/nature09386

Vancouver

Heinig M, Petretto E, Wallace C, Bottolo L, Rotival M, Lu H et al. A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk. NATURE. 2010 Sep 23;467(7314):460-464. https://doi.org/10.1038/nature09386

Bibtex

@article{f1b4d86c3233414fb031d7ed08c0ca5a,
title = "A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk",
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. 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.",
keywords = "Animals, Base Sequence, Chromosomes, Human, Pair 13/genetics, Chromosomes, Mammalian/genetics, Diabetes Mellitus, Type 1/genetics, Gene Regulatory Networks/genetics, Genetic Loci/genetics, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study, Humans, Immunity, Innate/genetics, Inflammation/genetics, Interferon Regulatory Factor-7/immunology, Macrophages/immunology, Organ Specificity, Polymorphism, Single Nucleotide/genetics, Quantitative Trait Loci/genetics, Rats, Receptors, G-Protein-Coupled/genetics, Viruses/immunology",
author = "Matthias Heinig and Enrico Petretto and Chris Wallace and Leonardo Bottolo and Maxime Rotival and Han Lu and Yoyo Li and Rizwan Sarwar and Langley, {Sarah R} and Anja Bauerfeind and Oliver Hummel and Young-Ae Lee and Svetlana Paskas and Carola Rintisch and Kathrin Saar and Jason Cooper and Rachel Buchan and Gray, {Elizabeth E} and Cyster, {Jason G} and Jeanette Erdmann and Christian Hengstenberg and Seraya Maouche and Ouwehand, {Willem H} and Rice, {Catherine M} and Samani, {Nilesh J} and Heribert Schunkert and Goodall, {Alison H} and Herbert Schulz and Roider, {Helge G} and Martin Vingron and Stefan Blankenberg and Thomas M{\"u}nzel and Tanja Zeller and Silke Szymczak and Andreas Ziegler and Laurence Tiret and Smyth, {Deborah J} and Michal Pravenec and Aitman, {Timothy J} and Francois Cambien and David Clayton and Todd, {John A} and Norbert Hubner and Cook, {Stuart A} and {CardioGenics Consortium}",
year = "2010",
month = sep,
day = "23",
doi = "10.1038/nature09386",
language = "English",
volume = "467",
pages = "460--464",
journal = "NATURE",
issn = "0028-0836",
publisher = "NATURE PUBLISHING GROUP",
number = "7314",

}

RIS

TY - JOUR

T1 - A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk

AU - Heinig, Matthias

AU - Petretto, Enrico

AU - Wallace, Chris

AU - Bottolo, Leonardo

AU - Rotival, Maxime

AU - Lu, Han

AU - Li, Yoyo

AU - Sarwar, Rizwan

AU - Langley, Sarah R

AU - Bauerfeind, Anja

AU - Hummel, Oliver

AU - Lee, Young-Ae

AU - Paskas, Svetlana

AU - Rintisch, Carola

AU - Saar, Kathrin

AU - Cooper, Jason

AU - Buchan, Rachel

AU - Gray, Elizabeth E

AU - Cyster, Jason G

AU - Erdmann, Jeanette

AU - Hengstenberg, Christian

AU - Maouche, Seraya

AU - Ouwehand, Willem H

AU - Rice, Catherine M

AU - Samani, Nilesh J

AU - Schunkert, Heribert

AU - Goodall, Alison H

AU - Schulz, Herbert

AU - Roider, Helge G

AU - Vingron, Martin

AU - Blankenberg, Stefan

AU - Münzel, Thomas

AU - Zeller, Tanja

AU - Szymczak, Silke

AU - Ziegler, Andreas

AU - Tiret, Laurence

AU - Smyth, Deborah J

AU - Pravenec, Michal

AU - Aitman, Timothy J

AU - Cambien, Francois

AU - Clayton, David

AU - Todd, John A

AU - Hubner, Norbert

AU - Cook, Stuart A

AU - CardioGenics Consortium

PY - 2010/9/23

Y1 - 2010/9/23

N2 - 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.

AB - 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.

KW - Animals

KW - Base Sequence

KW - Chromosomes, Human, Pair 13/genetics

KW - Chromosomes, Mammalian/genetics

KW - Diabetes Mellitus, Type 1/genetics

KW - Gene Regulatory Networks/genetics

KW - Genetic Loci/genetics

KW - Genetic Predisposition to Disease/genetics

KW - Genome-Wide Association Study

KW - Humans

KW - Immunity, Innate/genetics

KW - Inflammation/genetics

KW - Interferon Regulatory Factor-7/immunology

KW - Macrophages/immunology

KW - Organ Specificity

KW - Polymorphism, Single Nucleotide/genetics

KW - Quantitative Trait Loci/genetics

KW - Rats

KW - Receptors, G-Protein-Coupled/genetics

KW - Viruses/immunology

U2 - 10.1038/nature09386

DO - 10.1038/nature09386

M3 - SCORING: Journal article

C2 - 20827270

VL - 467

SP - 460

EP - 464

JO - NATURE

JF - NATURE

SN - 0028-0836

IS - 7314

ER -