A cross-disease meta-GWAS identifies four new susceptibility loci shared between systemic sclerosis and Crohn’s disease
Creators: name: González-Serna, David
name: Ochoa, Eguzkine
name: López-Isac, Elena
name: Julià, Antonio
name: Degenhardt, Frauke
name: Ortego-Centeno, Norberto
name: Radstake, Timothy R. D. J.
name: Franke, Andre
name: Marsal, Sara
name: Mayes, Maureen D.
name: Martín, Javier
name: Márquez, Ana
name: Assassi, Shervin
name: Zhou, Xiaodong
name: Tan, Filemon K.
name: Arnett, Frank C.
name: Reveille, John D.
name: Gorlova, Olga
name: Chen, Wei V.
name: Ying, Jun
name: Gregersen, Peter K.
name: Lee, Annette T.
name: Voskuyl, Alexandre E.
name: De Vries-Bouwstra, Jeska
name: Magro-Checa, Cesar
name: Broen, Jasper
name: Koeleman, Bobby P. C.
name: Simeón, Carmen P.
name: Fonollosa, Vicente
name: Guillén, Alfredo
name: Carreira, Patricia
name: Castellví, Iván
name: González-Gay, Miguel A.
name: Ríos, Raquel
name: Callejas-Rubio, Jose Luis
name: Vargas-Hitos, José A.
name: García-Portales, Rosa
name: Camps, María Teresa
name: Fernández-Nebro, Antonio
name: González-Escribano, María F.
name: García-Hernández, Francisco José
name: Castillo, Ma. Jesús
name: Aguirre, Ma. Ángeles
name: Gómez-Gracia, Inmaculada
name: Rodríguez-Rodríguez, Luis
name: Fernández-Gutiérrez, Benjamín
name: De La Peña, Paloma García
name: Vicente, Esther
name: Andreu, José Luis
name: Fernández De Castro, Mónica
name: López-Longo, Francisco Javier
name: Martínez, Lina
name: Espinosa, Gerard
name: Tolosa, Carlos
name: Pros, Anna
name: Rodríguez-Carballeira, Mónica
name: Narváez, Francisco Javier
name: Rubio-Rivas, Manel
name: Ortiz-Santamaría, Vera
name: Madroñero, Ana Belén
name: Díaz, Bernardino
name: Trapiella, Luis
name: Sousa, Adrián
name: Egurbide, María Victoria
name: Fanlo-Mateo, Patricia
name: Sáez-Comet, Luis
name: Díaz-González, Federico
name: Hernández, Vanesa
name: Beltrán, Emma
name: Román-Ivorra, José Andrés
name: Grau, Elena
name: Alegre-Sancho, Juan José
name: Blanco-García, Francisco J.
name: Oreiro, Natividad
name: Freire, Mayka
name: Balsa, Alejandro
name: Ortiz, Ana M.
name: Hunzelmann, Nicolas
name: Riemekasten, Gabriela
name: Distler, Jörg H. W.
name: Witte, Torsten
name: Airó, Paolo
name: Beretta, Lorenzo
name: Santaniello, Alessandro
name: Bellocchi, Chiara
name: Lunardi, Claudio
name: Moroncini, Gianluca
name: Gabrielli, Armando
Publisher: name: Apollo - University of Cambridge Repository
Year: 2020
Subjects: Article
/692/699/249/2510
/692/499
/45/43
/45
article

description: 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.