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

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • 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.
  • 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.

Grupos

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. © 2020, The Author(s).

Datos de la publicación

ISSN/ISSNe:
2045-2322, 2045-2322

Scientific Reports  NATURE PORTFOLIO

Tipo:
Article
Páginas:
-
PubMed:
32024964
Enlace a otro recurso:
www.scopus.com
Factor de Impacto:
1,240 SCImago ℠
Cuartil:
Q1 SCImago ℠

Documentos

  • No hay documentos

Métricas

Filiaciones mostrar / ocultar

Keywords

  • Case-Control Studies; Crohn Disease; Female; Gene Expression; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; Polymorphism, Single Nucleotide; Scleroderma, Systemic; case control study; Crohn disease; female; gene expression; gene locus; genetic predisposition; genetics; genome-wide association study; human; male; meta analysis; procedures; single nucleotide polymorphism; systemic sclerosis

Campos de Estudio

Cita

Compartir