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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, <jats:italic>IL12RB2<\/jats:italic>, <jats:italic>IRF1<\/jats:italic>\/<jats:italic>SLC22A5<\/jats:italic>, <jats:italic>STAT3<\/jats:italic> 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.<\/jats:p>","DOI":"10.1038\/s41598-020-58741-w","type":"journal-article","created":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T11:03:18Z","timestamp":1580900598000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["A cross-disease meta-GWAS identifies four new susceptibility loci shared between systemic sclerosis and Crohn\u2019s disease"],"prefix":"10.1038","volume":"10","author":[{"given":"David","family":"Gonz\u00e1lez-Serna","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eguzkine","family":"Ochoa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"L\u00f3pez-Isac","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6064-3620","authenticated-orcid":false,"given":"Antonio","family":"Juli\u00e0","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frauke","family":"Degenhardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norberto","family":"Ortego-Centeno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy R. 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