Causal association between genetically predicted primary aldosteronism and aortic aneurysm and aortic dissection: A Mendelian randomization study

Emerging research indicates a potential pathogenic overlap between primary aldosteronism (PA) and aortic aneurysm (AA)/aortic dissection (AD). Despite case reports suggest a potential link between PA and AA/AD, the causality of this relationship remains unclear. This study is the first to elucidate the causal association between genetically predicted PA and the risk of AA and AD through Mendelian randomization (MR) analysis. Genome-wide significant single nucleotide polymorphisms associated with PA were identified from publicly available genome-wide association study summary statistics. Genetic associations with AA and AD were obtained from the FinnGen database. The inverse-variance weighted (IVW) method, along with complementary MR analysis methods, was employed to generate primary estimates. Sensitivity analyses were performed to ensure the robustness of findings. MR analyses utilizing the IVW method revealed a significant causal association between genetically predicted PA and the risk of AA (OR = 1.038; 95% CI = 1.024-1.053; P < .01), thoracic AA (OR = 1.066; 95% CI = 1.045-1.087; P < .01) and AD (OR = 1.165; 95% CI = 1.113-1.219; P < .01). Conversely, no significant association was observed between PA and abdominal AA (OR = 1.013; 95% CI = 0.993-1.034; P = .210). There was no heterogeneity and horizontal pleiotropy in the MR analyses (P > .05). PA is genetically and causally associated with higher risks of AA and AD. More attention should be paid to the screening and treatment of PA to reduce the incidence of aortic diseases.