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

González-Serna D, Ochoa E, López-Isac E, Julià A, Degenhardt F, Ortego-Centeno N, Radstake TR, Franke A, Marsal S, Mayes MD, Martín J, Márquez A, Assassi S, Zhou X, Tan FK, Arnett FC, Reveille JD, Gorlova O, Chen WV, Ying J, Gregersen PK, Lee AT, Voskuyl AE, de Vries-Bouwstra J, Magro-Checa C, Broen J, Koeleman BP, Simeón CP, Fonollosa V, Guillén A, Carreira P, Castellví I, González-Gay MA, Ríos R, Callejas-Rubio JL, Vargas-Hitos JA, García-Portales R, Camps MT, Fernández-Nebro A, González-Escribano MF, García-Hernández FJ, Castillo MJ, Aguirre MÁ, Gómez-Gracia I, Rodríguez-Rodríguez L, Fernández-Gutiérrez B, de la Peña PG, Vicente E, Andreu JL, Fernández de Castro M, López-Longo FJ, Martínez L, Espinosa G, Tolosa C, Pros A, Rodríguez-Carballeira M, Narváez FJ, Rubio-Rivas M, Ortiz-Santamaría V, Madroñero AB, Díaz B, Trapiella L, Sousa A, Egurbide MV, Fanlo-Mateo P, Sáez-Comet L, Díaz-González F, Hernández V, Beltrán E, Román-Ivorra JA, Grau E, Alegre-Sancho JJ, Blanco-García FJ, Oreiro N, Freire M, Balsa A, Ortiz AM, Hunzelmann N, Riemekasten G, Distler J, Witte T, Airó P, Beretta L, Santaniello A, Bellocchi C, Lunardi C, Moroncini G, Gabrielli A (2020)

Publication Type: Journal article

Publication year: 2020


Book Volume: 10

Article Number: 1862

Journal Issue: 1

DOI: 10.1038/s41598-020-58741-w


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.

Authors with CRIS profile

Involved external institutions

Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron ES Spain (ES) Christian-Albrechts-Universität zu Kiel DE Germany (DE) Hospital Universitario San Cecilio ES Spain (ES) University of Texas Health Science Center at Houston (UTHealth) US United States (USA) (US) Institute of Parasitology and Biomedicine López-Neyra / Instituto de Parasitología y Biomedicina "López - Neyra" ES Spain (ES) Bellvitge University Hospital / Hospital Universitari de Bellvitge ES Spain (ES) Hospitales Universitarios Virgen Macarena y Virgen del Rocío ES Spain (ES) Leiden University Medical Center NL Netherlands (NL) Feinstein Institute for Medical Research US United States (USA) (US) Amsterdam University Medical Centers (Amsterdam UMC) / Amsterdam Universitair Medische Centra NL Netherlands (NL) Hospital Regional de Málaga ES Spain (ES) Hospital Universitario Puerta de Hierro - Majadahonda ES Spain (ES) Hospital General Universitario Gregorio Marañón ES Spain (ES) Hospital Clínico San Carlos ES Spain (ES) Universidad Autónoma de Madrid (UAM) ES Spain (ES) Hospital Universitario y Politécnico de La Fe ES Spain (ES) Hospital General Universitari de València ES Spain (ES) Complejo Hospitalario Universitario de Vigo (CHUVI) ES Spain (ES) Hospital Universitario de Canarias ES Spain (ES) Hospital Universitario La Paz ES Spain (ES) Università Politecnica delle Marche (UNIVPM) / Marche Polytechnic University IT Italy (IT) Charité - Universitätsmedizin Berlin DE Germany (DE) Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico IT Italy (IT) Hospital Parc Tauli ES Spain (ES) Hospital Universitario Virgen de la Victoria ES Spain (ES) University of A Coruña / Universidade da Coruña ES Spain (ES) Hospital Universitario Reina Sofía de Córdoba Edificio IMIBIC ES Spain (ES) Hospital de la Santa Creu i Sant Pau ES Spain (ES) Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia IT Italy (IT) Central University Hospital of Asturias ES Spain (ES) Complejo Hospitalario de Navarra - Hospital de Navarra ES Spain (ES) University Medical Centre Utrecht (UMC Utrecht) NL Netherlands (NL) Hospital General San Jorge ES Spain (ES) Hospital Universitario 12 de Octubre ES Spain (ES) Hospital Universitario de La Princesa ES Spain (ES) University of Verona / Università degli Studi di Verona IT Italy (IT) Hospital Universitario Miguel Servet ES Spain (ES) University of Texas MD Anderson Cancer Center US United States (USA) (US) Universitätsklinikum Köln DE Germany (DE) Universidad de Cantabria (UC) ES Spain (ES) Radboud University Nijmegen Medical Centre / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC) NL Netherlands (NL) Hospital del Mar ES Spain (ES) Gottfried Wilhelm Leibniz Universität Hannover DE Germany (DE) Hospital Asil de Granollers ES Spain (ES) Osakidetza ES Spain (ES) Hospital Clínic de Barcelona ES Spain (ES) Complejo Hospitalario Universitario de Granada ES Spain (ES) Hospital Universitario Dr. Peset Aleixandre ES Spain (ES)

How to cite


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


González-Serna, David, et al. "A cross-disease meta-GWAS identifies four new susceptibility loci shared between systemic sclerosis and Crohn’s disease." Scientific Reports 10.1 (2020).

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