Abstract
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.
Highlights
Autoimmune diseases are a group of highly disabling chronic disorders characterized by the activation of multiple immune and inflammatory pathways against the self [1]
The cohort of patients used for the present study included: (i) 1,281 rheumatoid arthritis (RA) patients that fulfilled the American College of Rheumatology (ACR) diagnostic criteria; (ii) 1,123 PS patients that were diagnosed based on the dermatologist clinical criteria; (iii) 989 psoriatic arthritis (PA) patients that fulfilled the Classification Criteria for Psoriatic Arthritis (CASPAR); (iv) 907 systemic lupus erythematosus (SLE) patients that fulfilled four or more of the 1982 revised ACR criteria for SLE classification; and (v) 2,185 inflammatory bowel diseases (IBDs) patients, including 1,358 and 827 patients that were diagnosed using the Lennard-Jones criteria as having Crohn’s disease (CD) and ulcerative colitis (UC), respectively (S1 File)
We successfully replicated the association between 17 genetic variants and cardiovascular diseases (CVD) risk in the different autoimmune diseases (P
Summary
Autoimmune diseases are a group of highly disabling chronic disorders characterized by the activation of multiple immune and inflammatory pathways against the self [1]. The estimated prevalence of autoimmunity is 5–7% in the general population [2]. Patients with autoimmune diseases have shown to have a higher risk to develop cardiovascular diseases (CVD) compared to the general population [3]. Understanding the genetic and biological mechanisms underlying CVD risk in autoimmunity could be fundamental to develop more efficient preventive and therapeutic strategies. Autoimmune diseases are genetically complex diseases [4]. In IBDs, for example, there are more than 160 risk loci known to be associated to these autoimmune diseases of the gut [6]. GWAS have enabled the identification of a shared genetic risk across autoimmune diseases [7]. Little is known yet about the genetic variation that contributes to clinically relevant phenotypes within each autoimmune disease
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call