English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/173608
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:


Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations

AuthorsMárquez, Ana; Kerick, Martin; Zhernakova, Alexandra; Gutierrez-Achury, Javier; Chen, Wei-Min; Onengut-Gumuscu, Suna; González-Álvaro, Isidoro; Rodríguez-Rodríguez, Luis; Ríos-Fernández, Raquel; González-Gay, M. A.; Mayes, Maureen D; Raychaudhuri, Soumya; Rich, Stephen S; Wijmenga, Cisca; Martín, J.
KeywordsCeliac disease
Rheumatoid arthritis
Systemic sclerosis
Type 1 diabetes
Cross-disease meta-analysis
Functional enrichment analysis
Autoimmune disease
Issue Date20-Dec-2018
PublisherBioMed Central
CitationGenome Medicine 10: 97 (2018)
Abstract[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. Cell-specific 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.
Publisher version (URL)https://doi.org/10.1186/s13073-018-0604-8
Appears in Collections:(IPBLN) Artículos
Files in This Item:
File Description SizeFormat 
13073_2018_Article_604.pdf1,61 MBAdobe PDFThumbnail
Show full item record
Review this work

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.