@misc{10481/60656,
year = {2020},
month = {2},
url = {http://hdl.handle.net/10481/60656},
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.},
organization = {This work was supported by the Spanish Ministry of Economy and Competitiveness (SAF2015-66761-P; IPT-010000-2010-36, cofunded by the European Regional Development Fund), Consejería de Innovación, Ciencia y Tecnología, Junta de Andalucía (Spain) (P12-BIO-1395) and the Cooperative Research Thematic Network (RETICS) programme (RD16/0012/0013) (RIER) from Instituto de Salud Carlos III (ISCIII, Spanish Ministry of Economy, Industry and Competitiveness). AM is recipient of a Miguel Servet fellowship (CP17/00008) from ISCIII (Spanish Ministry of Economy, Industry and Competitiveness). DGS was supported by the Spanish Ministry of Economy and Competitiveness through the FPI programme (SAF2015-66761-P). This work is part of the Doctoral Thesis “Bases Genéticas de la Esclerosis Sistémica: Integrando Genómica y Transcriptómica”.},
publisher = {Nature Research},
title = {A cross-disease meta-GWAS identifies four new susceptibility loci shared between systemic sclerosis and Crohn’s disease},
doi = {10.1038/s41598-020-58741-w},
author = {González-Serna, David and Ortego Centeno, Norberto and Márquez, Ana and Scleroderma Genetic Consortium},
}