RT Journal Article
T1 A cross-disease meta-GWAS identifies four new susceptibility loci shared between systemic sclerosis and Crohn's disease.
A1 Gonzalez-Serna, David
A1 Ochoa, Eguzkine
A1 Lopez-Isac, Elena
A1 Julia, Antonio
A1 Degenhardt, Frauke
A1 Ortego-Centeno, Norberto
A1 Radstake, Timothy R D J
A1 Franke, Andre
A1 Marsal, Sara
A1 Mayes, Maureen D
A1 Martin, Javier
A1 Marquez, Ana
K1 Inflammatory diseases
K1 Risk factors
AB 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.
PB Nature Publishing Group
YR 2019
FD 2019-12-19
LK http://hdl.handle.net/10668/15052
UL http://hdl.handle.net/10668/15052
LA en
NO González-Serna D, Ochoa E, López-Isac E, Julià A, Degenhardt F, Ortego-Centeno N, et al. A cross-disease meta-GWAS identifies four new susceptibility loci shared between systemic sclerosis and Crohn's disease. Sci Rep. 2020 Feb 5;10(1):1862.
DS RISalud
RD Apr 10, 2025