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

Overview of attention for article published in Arthritis Research & Therapy, June 2017
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  • Above-average Attention Score compared to outputs of the same age (51st percentile)

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4 tweeters
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1 Facebook page

Citations

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14 Dimensions

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45 Mendeley
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Title
Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus
Published in
Arthritis Research & Therapy, June 2017
DOI 10.1186/s13075-017-1345-6
Pubmed ID
Authors

Adrià Aterido, Antonio Julià, Patricia Carreira, Ricardo Blanco, José Javier López-Longo, José Javier Pérez Venegas, Àlex Olivé, José Luís Andreu, Maria Ángeles Aguirre-Zamorano, Paloma Vela, Joan M. Nolla, José Luís Marenco-de la Fuente, Antonio Zea, José María Pego, Mercedes Freire, Elvira Díez, María López-Lasanta, Mireia López-Corbeto, Núria Palau, Raül Tortosa, Josep Lluís Gelpí, Devin Absher, Richard M Myers, Antonio Fernández-Nebro, Sara Marsal

Abstract

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.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 45 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 7 16%
Student > Master 6 13%
Researcher 6 13%
Other 5 11%
Student > Doctoral Student 4 9%
Other 8 18%
Unknown 9 20%
Readers by discipline Count As %
Medicine and Dentistry 18 40%
Biochemistry, Genetics and Molecular Biology 6 13%
Psychology 4 9%
Agricultural and Biological Sciences 1 2%
Immunology and Microbiology 1 2%
Other 4 9%
Unknown 11 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 July 2017.
All research outputs
#10,171,412
of 18,008,158 outputs
Outputs from Arthritis Research & Therapy
#1,636
of 2,643 outputs
Outputs of similar age
#128,110
of 276,516 outputs
Outputs of similar age from Arthritis Research & Therapy
#1
of 1 outputs
Altmetric has tracked 18,008,158 research outputs across all sources so far. This one is in the 42nd percentile – i.e., 42% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,643 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.5. This one is in the 36th percentile – i.e., 36% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 276,516 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them