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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations
Genome Medicine, Volume 10, No. 1, Article 97, Year 2018
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Description
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. © 2018 The Author(s).
Authors & Co-Authors
Márquez, Ana
Spain, Madrid
Consejo Superior de Investigaciones Científicas
Spain, Granada
Instituto de Investigación Biosanitaria de Granada
Kerick, Martin
Spain, Madrid
Consejo Superior de Investigaciones Científicas
Zhernakova, Alexandra
Netherlands, Groningen
Rijksuniversiteit Groningen
Gutiérrez-Achury, Javier
United Kingdom, Hinxton
Wellcome Sanger Institute
Chen, Weimin
United States, Charlottesville
University of Virginia
Önengüt-Gümüşcü, Suna
United States, Charlottesville
University of Virginia
Rodríguez-Rodríguez, Luís Pablo
Spain, Madrid
Hospital Clínico San Carlos
González-Gay, Miguel Ángel
Spain, Santander
Epidemiology
Mayes, Maureen Davidica
United States, Houston
University of Texas Health Science Center at Houston
Raychaudhuri, Soumya
United States, Boston
Harvard Medical School
United States, Cambridge
Massachusetts Institute of Technology
Rich, Stephen S.
United States, Charlottesville
University of Virginia
Wijmenga, Cisca
Netherlands, Groningen
Rijksuniversiteit Groningen
Martin, Javier
Spain, Madrid
Consejo Superior de Investigaciones Científicas
Statistics
Citations: 62
Authors: 13
Affiliations: 11
Identifiers
Doi:
10.1186/s13073-018-0604-8
ISSN:
1756994X
Research Areas
Genetics And Genomics
Noncommunicable Diseases
Study Approach
Systematic review