The causal relationship between immune-mediated inflammatory diseases
and aortic aneurysm: A bidirectional two-sample Mendelian randomization
study
Abstract
Introduction: Many observational studies have identified aortic
aneurysm (AA) as a cardiovascular complication of immune-mediated
inflammatory diseases (IMIDs). However, due to the effects of various
confounders, it is still uncertainty whether this association holds or
whether reverse causality is involved. Here we conducted a two-sample
bidirectional MR study to infer the causal relationships between the two
diseases. Method: We obtained genetic association datasets from
public GWAS databases in populations of European ancestry. Abiding by
the assumptions of Mendelian randomization (MR), we selected valid
instrumental variables from genetic variants. Different statistic
methods were performed for MR analysis and sensitivity analysis, and the
inverse variance weighted (IVW) method was regarded as the most
efficient estimate of the causal effect in this study. Results:
The IVW method found evidence that genetically predicted AA had a causal
effect on rheumatoid arthritis (RA) (OR = 1.06, 95%CI = 1.01-1.12,
p = 0.029), but not of RA or other IMIDs on AA. Besides, no
evidence showed that AA may increase the risk of inflammatory bowel
disease (IBD), Crohn’s disease (CD), ulcerative colitis (UC), systemic
lupus erythematosus (SLE) and psoriasis (PSO). The sensitivity analysis
confirmed the absence of heterogeneity or horizontal pleiotropy effect.
Conclusion: In summary, our study discovered that genetically
predicted AA may increase the risk of RA, while no evidence was found
that patients with RA had an increased risk of AA. Furthermore, we
confirmed no evidence of association between IBD, CD, UC, SLE, PSO and
AA. This is in accordance with other reports that demonstrated the human
leukocyte antigen molecule in inflammatory aortic aneurysm was a genetic
risk loci. Our study provides directions for future research on genetic
susceptibility to inflammatory aortic aneurysm.