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dc.contributor.authorMárquez, Ana
dc.contributor.authorKerick, Martin
dc.contributor.authorZhernakova, Alexandra
dc.contributor.authorGutierrez-Achury, Javier
dc.contributor.authorChen, Wei-Min
dc.contributor.authorOnengut-Gumuscu, Suna
dc.contributor.authorGonzález-Álvaro, Isidoro
dc.contributor.authorRodriguez-Rodriguez, Luis
dc.contributor.authorRios-Fernández, Raquel
dc.contributor.authorGonzález-Gay, Miguel A
dc.contributor.authorCoeliac Disease Immunochip Consortium
dc.contributor.authorRheumatoid Arthritis Consortium International for Immunochip (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, Javier
dc.description.abstractBACKGROUND: 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.
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.subjectCoeliac Disease Immunochip Consortium
dc.subjectRheumatoid Arthritis Consortium International for Immunochip (RACI)
dc.subjectInternational Scleroderma Group
dc.subjectType 1 Diabetes Genetics Consortium
dc.subjectArthritis, Rheumatoid
dc.subjectCeliac Disease
dc.subjectScleroderma, Systemic
dc.subjectDiabetes Mellitus, Type 1
dc.subjectAutoimmune Diseases
dc.subjectGenetic Predisposition to Disease
dc.subjectPolymorphism, Single Nucleotide
dc.subjectGenome-Wide Association Study
dc.subjectMolecular Sequence Annotation
dc.titleMeta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations.
prism.publicationNameGenome Med
dc.contributor.orcidMárquez, Ana [0000-0001-9913-7688]
rioxxterms.typeJournal Article/Review
pubs.funder-project-idNational Institute of Diabetes and Digestive and Kidney Diseases (U01DK062418)

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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International