دورية أكاديمية
Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations
| العنوان: | Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations |
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| المؤلفون: | Márquez, 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. |
| المساهمون: | Ministerio de Economía y Competitividad (España), Junta de Andalucía, Instituto de Salud Carlos III, European Commission |
| بيانات النشر: | BioMed Central |
| سنة النشر: | 2018 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | Celiac disease, Rheumatoid arthritis, Systemic sclerosis, Type 1 diabetes, Cross-disease meta-analysis, Immunochip, Functional enrichment analysis, Autoimmune diseases |
| الوصف: | [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. ; This 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 1756-994X |
| العلاقة: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-66761-P; info:eu-repo/grantAgreement/EC/FP7/2012–322698; Publisher's version; https://doi.org/10.1186/s13073-018-0604-8Test; Sí; Genome Medicine 10: 97 (2018); http://hdl.handle.net/10261/173608Test; http://dx.doi.org/10.13039/501100004587Test; http://dx.doi.org/10.13039/501100000780Test; http://dx.doi.org/10.13039/501100003329Test; http://dx.doi.org/10.13039/501100011011Test |
| DOI: | 10.1186/s13073-018-0604-8 |
| DOI: | 10.13039/501100004587 |
| DOI: | 10.13039/501100000780 |
| DOI: | 10.13039/501100003329 |
| DOI: | 10.13039/501100011011 |
| الإتاحة: | https://doi.org/10.1186/s13073-018-0604-8Test https://doi.org/10.13039/501100004587Test https://doi.org/10.13039/501100000780Test https://doi.org/10.13039/501100003329Test https://doi.org/10.13039/501100011011Test http://hdl.handle.net/10261/173608Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.B2E7E805 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 1756994X |
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| DOI: | 10.1186/s13073-018-0604-8 |