A cross-disease meta-GWAS identifies four new susceptibility loci shared between systemic sclerosis and Crohn's disease

Autor: González-Serna, David, Ochoa, Eguzkine, López-Isac, Elena, Julià, Antonio, Degenhardt, Frauke, Ortego-Centeno, Norberto, Radstake, Timothy R.D.J., Franke, Andre, Marsal, Sara, Mayes, Maureen D., Martín, Javier, Márquez, Ana, Assassi, Shervin, Zhou, Xiaodong, Tan, Filemon K., Arnett, Frank C., Reveille, John D., Gorlova, Olga, Chen, Wei V., Ying, Jun, Gregersen, Peter K., Lee, Annette T., Voskuyl, Alexandre E., de Vries-Bouwstra, Jeska, Magro-Checa, Cesar, Broen, Jasper, Koeleman, Bobby P.C., Simeón, Carmen P., Fonollosa, Vicente, Guillén, Alfredo, Carreira, Patricia, Castellví, Iván, González-Gay, Miguel A., Ríos, Raquel, Callejas-Rubio, Jose Luis, Vargas-Hitos, José A., García-Portales, Rosa, Camps, María Teresa, Fernández-Nebro, Antonio, González-Escribano, María F., García-Hernández, Francisco José, Castillo, Ma Jesús, Aguirre, Ma Ángeles, Gómez-Gracia, Inmaculada, Rodríguez-Rodríguez, Luis, Fernández-Gutiérrez, Benjamín, de la Peña, Paloma García, Vicente, Esther, Andreu, José Luis, Fernández de Castro, Mónica, López-Longo, Francisco Javier, Martínez, Lina, Espinosa, Gerard, Tolosa, Carlos, Pros, Anna, Rodríguez-Carballeira, Mónica, Narváez, Francisco Javier, Rubio-Rivas, Manel, Ortiz-Santamaría, Vera, Madroñero, Ana Belén, Díaz, Bernardino, Trapiella, Luis, Sousa, Adrián, Egurbide, María Victoria, Fanlo-Mateo, Patricia, Sáez-Comet, Luis, Díaz-González, Federico, Hernández, Vanesa, Beltrán, Emma, Román-Ivorra, José Andrés, Grau, Elena, Alegre-Sancho, Juan José, Blanco-García, Francisco J., Oreiro, Natividad, Freire, Mayka, Balsa, Alejandro, Ortiz, Ana M., Hunzelmann, Nicolas, Riemekasten, Gabriela, Distler, Jörg H.W., Witte, Torsten, Airó, Paolo, Beretta, Lorenzo, Santaniello, Alessandro, Bellocchi, Chiara, Lunardi, Claudio, Moroncini, Gianluca, Gabrielli, Armando
Přispěvatelé: Universidad de Salamanca, Junta de Andalucía, Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad (España), Ministerio de Economía y Competitividad (España), Rheumatology, AII - Inflammatory diseases, Julià, Antonio [0000-0001-6064-3620], Franke, Andre [0000-0003-1530-5811], Mayes, Maureen D [0000-0001-5070-2535], Apollo - University of Cambridge Repository, Mayes, Maureen D. [0000-0001-5070-2535], Universidad de Cantabria
Rok vydání: 2020
Předmět:
Zdroj: Scientific Reports, 10(1):1862. Nature Publishing Group
Scientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
González-Serna, D, Ochoa, E, López-Isac, E, Julià, A, Degenhardt, F, Ortego-Centeno, N, Radstake, T R D J, Franke, A, Marsal, S, Mayes, M D, Martín, J, Márquez, A, Assassi, S, Zhou, X, Tan, F K, Arnett, F C, Reveille, J D, Gorlova, O, Chen, W V, Ying, J, Gregersen, P K, Lee, A T, Voskuyl, A E, de Vries-Bouwstra, J, Magro-Checa, C, Broen, J, Koeleman, B P C, Simeón, C P, Fonollosa, V, Guillén, A, Carreira, P, Castellví, I, González-Gay, M A, Ríos, R, Callejas-Rubio, J L, Vargas-Hitos, J A, García-Portales, R, Camps, M T, Fernández-Nebro, A, González-Escribano, M F, García-Hernández, F J, Castillo, M J, Aguirre, M Á, Gómez-Gracia, I, Rodríguez-Rodríguez, L, Fernández-Gutiérrez, B, de la Peña, P G, Vicente, E, Andreu, J L, Fernández de Castro, M, López-Longo, F J, Martínez, L, Espinosa, G, Tolosa, C, Pros, A, Rodríguez-Carballeira, M, Narváez, F J, Rubio-Rivas, M, Ortiz-Santamaría, V, Madroñero, A B, Díaz, B, Trapiella, L, Sousa, A, Egurbide, M V, Fanlo-Mateo, P, Sáez-Comet, L, Díaz-González, F, Hernández, V, Beltrán, E, Román-Ivorra, J A, Grau, E, Alegre-Sancho, J J, Blanco-García, F J, Oreiro, N, Freire, M, Balsa, A, Ortiz, A M, Hunzelmann, N, Riemekasten, G, Distler, J H W, Witte, T, Airó, P, Beretta, L, Santaniello, A, Bellocchi, C, Lunardi, C, Moroncini, G, Gabrielli, A & Scleroderma Genetic Consortium 2020, ' A cross-disease meta-GWAS identifies four new susceptibility loci shared between systemic sclerosis and Crohn’s disease ', Scientific Reports, vol. 10, no. 1, 1862 . https://doi.org/10.1038/s41598-020-58741-w
Digital.CSIC. Repositorio Institucional del CSIC
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Digibug. Repositorio Institucional de la Universidad de Granada
Scientific Reports
Scientific Reports (2020) 10:1862
UCrea Repositorio Abierto de la Universidad de Cantabria
Universidad de Cantabria (UC)
ISSN: 2045-2322
DOI: 10.1038/s41598-020-58741-w
Popis: We thank Sofia Vargas and Gema Robledo for her excellent technical assistance and all the patients and control donors for their essential collaboration. We thank WTCCC (Welcome Trust Case Control Consortium) for the access to GWAS data of Crohn’s disease patients and healthy controls, Banco Nacional de ADN (University of Salamanca, Spain) who supplied part of the control DNA samples, and dbGap for granting access to the IBD Genetics Consortium (IBDGC) Crohn’s Disease GWAS data (phs000130.v1.p1). The IBDGC Crohn’s Disease Genome-Wide Association Study was conducted by the IBDGC Investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). This manuscript was not prepared in collaboration with Investigators of the IBDGC Crohn’s Disease Genome-Wide Association Study and does not necessarily reflect the opinions or views of the IBDGC Crohn’s Disease Genome-Wide Association Study, the NIDDK Central Repositories, or the NIDDK.
Genome-wide association studies (GWASs) have identified a number of genetic risk loci associated with systemic sclerosis (SSc) and Crohn’s disease (CD), some of which confer susceptibility to both diseases. In order to identify new risk loci shared between these two immune-mediated disorders, we performed a cross-disease meta-analysis including GWAS data from 5,734 SSc patients, 4,588 CD patients and 14,568 controls of European origin. We identified 4 new loci shared between SSc and CD, IL12RB2, IRF1/SLC22A5, STAT3 and an intergenic locus at 6p21.31. Pleiotropic variants within these loci showed opposite allelic effects in the two analysed diseases and all of them showed a significant effect on gene expression. In addition, an enrichment in the IL-12 family and type I interferon signaling pathways was observed among the set of SSc-CD common genetic risk loci. In conclusion, through the first cross-disease meta-analysis of SSc and CD, we identified genetic variants with pleiotropic effects on two clinically distinct immune-mediated disorders. The fact that all these pleiotropic SNPs have opposite allelic effects in SSc and CD reveals the complexity of the molecular mechanisms by which polymorphisms affect diseases.
This work was supported by the Spanish Ministry of Economy and Competitiveness (SAF2015-66761-P; IPT-010000-2010-36, cofunded by the European Regional Development Fund), Consejería de Innovación, Ciencia y Tecnología, Junta de Andalucía (Spain) (P12-BIO-1395) and the Cooperative Research Thematic Network (RETICS) programme (RD16/0012/0013) (RIER) from Instituto de Salud Carlos III (ISCIII, Spanish Ministry of Economy, Industry and Competitiveness). AM is recipient of a Miguel Servet fellowship (CP17/00008) from ISCIII (Spanish Ministry of Economy, Industry and Competitiveness). DGS was supported by the Spanish Ministry of Economy and Competitiveness through the FPI programme (SAF2015-66761-P). This work is part of the Doctoral Thesis “Bases Genéticas de la Esclerosis Sistémica: Integrando Genómica y Transcriptómica”.
Databáze: OpenAIRE
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