Genetic variation associated with cardiovascular risk in autoimmune diseases

Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD) risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoim...

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Bibliographic Details
Published in:PloS one 2017-10, Vol.12 (10), p.e0185889-e0185889
Main Authors: Perrotti, Pedro P, Aterido, Adrià, Fernández-Nebro, Antonio, Cañete, Juan D, Ferrándiz, Carlos, Tornero, Jesús, Gisbert, Javier P, Domènech, Eugeni, Fernández-Gutiérrez, Benjamín, Gomollón, Fernando, García-Planella, Esther, Fernández, Emilia, Sanmartí, Raimon, Gratacós, Jordi, Martínez-Taboada, Víctor Manuel, Rodríguez-Rodríguez, Luís, Palau, Núria, Tortosa, Raül, Corbeto, Mireia L, Lasanta, María L, Marsal, Sara, Julià, Antonio
Format: Article
Language:English
Subjects:
Atherosclerosis
Autoimmune diseases
Autoimmune Diseases - complications
Biology and Life Sciences
Cardiovascular diseases
Cardiovascular Diseases - etiology
Cardiovascular Diseases - genetics
Cluster analysis
Consortia
Data processing
Development and progression
Disease
Disease susceptibility
Economic impact
Etiology
Female
Genetic analysis
Genetic aspects
Genetic diversity
Genetic effects
Genetic Predisposition to Disease
Genetic Variation
Genetics
Genomes
Genotyping
Genètica
Health risks
Hospitals
Humans
Immunology
Impact analysis
Loci
Lupus
Malalties autoimmunitàries
Malalties cardiovasculars
Male
Medicine and Health Sciences
Pathways
Polymorphism, Single Nucleotide
Population
Rheumatoid arthritis
Rheumatology
Risk analysis
Risk factors
TNF inhibitors
Tumor necrosis factor-TNF
Tumor necrosis factor-α
γ-Interferon
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Summary:Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD) risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoimmune diseases that are associated with a high socio-economic impact. First, for each disease, we tested the association of established CVD risk loci. Second, we analyzed the association of autoimmune disease susceptibility loci with CVD. Finally, to identify genetic patterns associated with CVD risk, we applied the cross-phenotype meta-analysis approach (CPMA) on the genome-wide data. A total of 17 established CVD risk loci were significantly associated with CVD in the autoimmune patient cohorts. From these, four loci were found to have significantly different genetic effects across autoimmune diseases. Six autoimmune susceptibility loci were also found to be associated with CVD risk. Genome-wide CPMA analysis identified 10 genetic clusters strongly associated with CVD risk across all autoimmune diseases. Two of these clusters are highly enriched in pathways previously associated with autoimmune disease etiology (TNFα and IFNγ cytokine pathways). The results of this study support the presence of specific genetic variation associated with the increase of CVD risk observed in autoimmunity.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0185889