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dc.contributor.authorMáquez Ortiz, Ana María
dc.contributor.authorKerick, Martin
dc.contributor.authorZhernakova, Alexandra
dc.contributor.authorGutiérrez Achury, Javier
dc.contributor.authorChen, Wei-Min
dc.contributor.authorOnengut Gumuscu, Suna
dc.contributor.authorGonzález Álvaro, Isidoro
dc.contributor.authorRodríguez Rodríguez, Luis
dc.contributor.authorRíos Fernández, Raquel
dc.contributor.authorGonzález-Gay Mantecón, Miguel Ángel 
dc.contributor.authorCoeliac Disease Immunochip Consortium
dc.contributor.authorRheumatoid Arthritis Consortium International (RACI)
dc.contributor.authorInternational Scleroderma Group
dc.contributor.authorType 1 Diabetes Genetics Consortium
dc.contributor.authorMayes, Maureen D.
dc.contributor.authorRaychaudhuri, Soumya
dc.contributor.authorRich, Stephen S.
dc.contributor.authorWijmenga, Cisca
dc.contributor.authorMartín Ibáñez, Javier
dc.contributor.otherUniversidad de Cantabriaes_ES
dc.description.abstractABSTRACT: Background: In recent years, research has consistently proven the occurrence of genetic overlap across autoimmune diseases, which supports the existence of common pathogenic mechanisms in autoimmunity. The objective of this study was to further investigate this shared genetic component. Methods: For this purpose, we performed a cross-disease meta-analysis of Immunochip data from 37,159 patients diagnosed with a seropositive autoimmune disease (11,489 celiac disease (CeD), 15,523 rheumatoid arthritis (RA), 3477 systemic sclerosis (SSc), and 6670 type 1 diabetes (T1D)) and 22,308 healthy controls of European origin using the R package ASSET. Results: We identified 38 risk variants shared by at least two of the conditions analyzed, five of which represent new pleiotropic loci in autoimmunity. We also identified six novel genome-wide associations for the diseases studied. Cellspecific functional annotations and biological pathway enrichment analyses suggested that pleiotropic variants may act by deregulating gene expression in different subsets of T cells, especially Th17 and regulatory T cells. Finally, drug repositioning analysis evidenced several drugs that could represent promising candidates for CeD, RA, SSc, and T1D treatment. Conclusions: In this study, we have been able to advance in the knowledge of the genetic overlap existing in autoimmunity, thus shedding light on common molecular mechanisms of disease and suggesting novel drug targets that could be explored for the treatment of the autoimmune diseases studied.es_ES
dc.description.sponsorshipThis work was supported by the following grants: SAF2015-66761-P from the Spanish Ministry of Economy and Competitiveness, P12-BIO-1395 from Consejería de Innovación, Ciencia y Tecnología, Junta de Andalucía (Spain), PI0493-2016 from Consejería de Salud, Junta de Andalucía (Spain) 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 a recipient of a Miguel Servet fellowship (CP17/00008) from ISCIII (Spanish Ministry of Economy, Industry and Competitiveness). CW is supported by FP7/2007-2013/ERC Advanced Grant (agreement 2012–322698), the Stiftelsen K.G. Jebsen Coeliac Disease Research Centre (Oslo, Norway), and a Spinoza Prize from the Netherlands Organization for Scientific Research (NWO SPI 92-266). This research utilizes resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD), and Juvenile Diabetes Research Foundation International (JDRF) and supported by U01 DK062418es_ES
dc.format.extent13 p.es_ES
dc.publisherBioMed Centrales_ES
dc.rightsAttribution 4.0 Internationales_ES
dc.sourceGenome Medicine (2018) 10:97es_ES
dc.subject.otherCeliac diseasees_ES
dc.subject.otherRheumatoid arthritises_ES
dc.subject.otherSystemic sclerosises_ES
dc.subject.otherType 1 diabeteses_ES
dc.subject.otherCross-disease meta-analysises_ES
dc.subject.otherAutoimmune diseasees_ES
dc.subject.otherFunctional enrichment analysises_ES
dc.titleMeta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associationses_ES

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Attribution 4.0 InternationalExcept where otherwise noted, this item's license is described as Attribution 4.0 International