Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus

Includes supplementary materials for the online appendix.

Bibliographic Details
Authors: Aterido Ballonga, Adrià, 1990-, Julià Cano, Antoni, Marsal Barril, Sara
Format: article
Status:Published version
Publication Date:2017
Country:España
Institution:Universitat Pompeu Fabra
Repository:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/57335
Online Access:http://hdl.handle.net/10230/57335
http://dx.doi.org/10.1186/s13075-017-1345-6
Access Level:Open access
Keyword:Genome-wide pathway analysis
Genetics
Systemic lupus erythematosus
Oral ulceration
Clinical phenotypes
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spelling Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosusAterido Ballonga, Adrià, 1990-Julià Cano, AntoniMarsal Barril, SaraGenome-wide pathway analysisGeneticsSystemic lupus erythematosusOral ulcerationClinical phenotypesIncludes supplementary materials for the online appendix.Systemic lupus erythematosus (SLE) is a genetically complex rheumatic disease characterized by heterogeneous clinical manifestations of unknown etiology. Recent studies have suggested the existence of a genetic basis for SLE heterogeneity. The objective of the present study was to identify new genetic variation associated with the clinically relevant phenotypes in SLE. A two-stage pathway-based approach was used to identify the genetic variation associated with the main clinical phenotypes in SLE. In the discovery stage, 482 SLE patients were genotyped using Illumina Human Quad610 microarrays. Association between 798 reference genetic pathways from the Molecular Signatures Database and 11 SLE phenotypes was tested using the set-based method implemented in PLINK software. Pathways significantly associated after multiple test correction were subsequently tested for replication in an independent cohort of 425 SLE patients. Using an in silico approach, we analyzed the functional effects of common SLE therapies on the replicated genetic pathways. The association of known SLE risk variants with the development of the clinical phenotypes was also analyzed. In the discovery stage, we found a significant association between the vascular endothelial growth factor (VEGF) pathway and oral ulceration (P value for false discovery rate (P FDR) < 0.05), and between the negative regulation signaling pathway of retinoic acid inducible gene-I/melanoma differentiation associated gene 5 and the production of antinuclear antibodies (P FDR < 0.05). In the replication stage, we validated the association between the VEGF pathway and oral ulceration. Therapies commonly used to treat mucocutaneous phenotypes in SLE were found to strongly influence VEGF pathway gene expression (P = 4.60e-4 to 5.38e-14). Analysis of known SLE risk loci identified a strong association between PTPN22 and the risk of hematologic disorder and with the development of antinuclear antibodies. The present study has identified VEGF genetic pathway association with the risk of oral ulceration in SLE. New therapies targeting the VEGF pathway could be more effective in reducing the severity of this phenotype. These findings represent a first step towards the understanding of the genetic basis of phenotype heterogeneity in SLE.BioMed Central202320232017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/57335http://dx.doi.org/10.1186/s13075-017-1345-6reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésArthritis Research & Therapy. 2017 Jun 15;19:138https://doi.org/10.6084/m9.figshare.c.3804598_D1.v1This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.http://creativecommons.org/publicdomain/zero/1.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/573352026-06-12T07:21:37Z
dc.title.none.fl_str_mv Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus
title Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus
spellingShingle Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus
Aterido Ballonga, Adrià, 1990-
Genome-wide pathway analysis
Genetics
Systemic lupus erythematosus
Oral ulceration
Clinical phenotypes
title_short Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus
title_full Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus
title_fullStr Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus
title_full_unstemmed Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus
title_sort Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus
dc.creator.none.fl_str_mv Aterido Ballonga, Adrià, 1990-
Julià Cano, Antoni
Marsal Barril, Sara
author Aterido Ballonga, Adrià, 1990-
author_facet Aterido Ballonga, Adrià, 1990-
Julià Cano, Antoni
Marsal Barril, Sara
author_role author
author2 Julià Cano, Antoni
Marsal Barril, Sara
author2_role author
author
dc.subject.none.fl_str_mv Genome-wide pathway analysis
Genetics
Systemic lupus erythematosus
Oral ulceration
Clinical phenotypes
topic Genome-wide pathway analysis
Genetics
Systemic lupus erythematosus
Oral ulceration
Clinical phenotypes
description Includes supplementary materials for the online appendix.
publishDate 2017
dc.date.none.fl_str_mv 2017
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/57335
http://dx.doi.org/10.1186/s13075-017-1345-6
url http://hdl.handle.net/10230/57335
http://dx.doi.org/10.1186/s13075-017-1345-6
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Arthritis Research & Therapy. 2017 Jun 15;19:138
https://doi.org/10.6084/m9.figshare.c.3804598_D1.v1
dc.rights.none.fl_str_mv http://creativecommons.org/publicdomain/zero/1.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/publicdomain/zero/1.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812455

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