Causal associations between 17 common autoimmune diseases and aortic diseases: a Mendelian randomization study

Previous studies have identified correlations between autoimmune and aortic diseases; however, the causal connection between these conditions remains uncertain and lack of comprehensiveness. This study aimed to investigate the potential causal relationships between autoimmune and aortic diseases from a genetic perspective.

A two-sample Mendelian randomization (MR) study was implemented to investigate the relationships between 17 common autoimmune diseases and aortic diseases. To serve as instrumental variables (IVs), we extracted single-nucleotide polymorphisms from both the genome-wide association study and the FinnGen databases. The inverse-variance weighted (IVW) approach was primarily employed to estimate causal links between autoimmune and aortic diseases. Several quality control assessments were conducted to maintain the rigor of the research, including heterogeneity tests, pleiotropy analyses, and sensitivity analyses.

Our MR study revealed a link between Addison's disease and an elevated risk of thoracic aortic aneurysm. In addition, Sjögren's syndrome and polymyalgia rheumatica showed negative and positive correlations with aortic dissection respectively. Although each of these two correlations was not statistically significant in the alternative sensitivity analysis, the estimates were in the same direction. No signs of horizontal heterogeneity or pleiotropy were detected in sensitivity analyses among these associations. The remaining 14 autoimmune diseases did not demonstrate a causal relationship with aortic diseases.

An increasing risk of thoracic aortic aneurysms may be related to Addison's disease. In addition, Sjögren's syndrome exhibited a negative association, while polymyalgia rheumatica exhibited a positive association with aortic dissection.