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

David González-Serna, Eguzkine Ochoa, Elena López-Isac, Antonio Julià, Frauke Degenhardt, Norberto Ortego-Centeno, Timothy R.D.J. Radstake, Andre Franke, Sara Marsal, Maureen D. Mayes, Javier Martín, Ana Márquez, Shervin Assassi, Xiaodong Zhou, Filemon K. Tan, Frank C. Arnett, John D. Reveille, Olga Gorlova, Wei V. Chen, Jun YingPeter K. Gregersen, Annette T. Lee, Alexandre E. Voskuyl, Jeska de Vries-Bouwstra, Cesar Magro-Checa, Jasper Broen, Bobby P.C. Koeleman, Carmen P. Simeón, Vicente Fonollosa, Alfredo Guillén, Patricia Carreira, Iván Castellví, Miguel A. González-Gay, Raquel Ríos, Jose Luis Callejas-Rubio, José A. Vargas-Hitos, Rosa García-Portales, María Teresa Camps, Antonio Fernández-Nebro, María F. González-Escribano, Francisco José García-Hernández, Ma Jesús Castillo, Ma Ángeles Aguirre, Inmaculada Gómez-Gracia, Luis Rodríguez-Rodríguez, Benjamín Fernández-Gutiérrez, Paloma García de la Peña, Esther Vicente, José Luis Andreu, Mónica Fernández de Castro, Francisco Javier López-Longo, Lina Martínez, Gerard Espinosa, Carlos Tolosa, Anna Pros, Mónica Rodríguez-Carballeira, Francisco Javier Narváez, Manel Rubio-Rivas, Vera Ortiz-Santamaría, Ana Belén Madroñero, Bernardino Díaz, Luis Trapiella, Adrián Sousa, María Victoria Egurbide, Patricia Fanlo-Mateo, Luis Sáez-Comet, Federico Díaz-González, Vanesa Hernández, Emma Beltrán, José Andrés Román-Ivorra, Elena Grau, Juan José Alegre-Sancho, Francisco J. Blanco-García, Natividad Oreiro, Mayka Freire, Alejandro Balsa, Ana M. Ortiz, Nicolas Hunzelmann, Gabriela Riemekasten, Jörg H.W. Distler, Torsten Witte, Paolo Airó, Lorenzo Beretta, Alessandro Santaniello, Chiara Bellocchi, Claudio Lunardi, Gianluca Moroncini, Armando Gabrielli, Scleroderma Genetic Consortium

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article number1862
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2020

Cite this

González-Serna, D., Ochoa, E., López-Isac, E., Julià, A., Degenhardt, F., Ortego-Centeno, N., ... Scleroderma Genetic Consortium (2020). A cross-disease meta-GWAS identifies four new susceptibility loci shared between systemic sclerosis and Crohn’s disease. Scientific Reports, 10(1), [1862]. https://doi.org/10.1038/s41598-020-58741-w