Causal associations of mental health disorders with aortic and peripheral vascular disease: a bi-directional two- sample mendelian randomization study

Abstract Background The actual causality between mental health disorders (MHD) with aorta and peripheral vascular disease (APVD) has not been established for the limited researches and the potential confounding factors. Methods Bi-directional two-sample Mendelian randomization (MR) analysis was performed to investigate evidence of causality and direction of 4 MHD (schizophrenia, anxiety disorder (AD), bipolar disorder (BD), and major depression disorder (MDD)) with 18 common APVD. Summary-level genetic statistics for MHD were obtained from Psychiatric Genomics Consortium, and APVD from FinnGen Project database. The inverse-variance weighted method was used for the primary MR analyses. Sensitivity analysis was also performed for heterogeneity and pleiotropy tests. Results Genetically-predicted schizophrenia was associated with increased risk of varicose veins [Odds Ratio (OR): 1.05; 95%confidential interval (CI): 1.01 to 1.09, P = 0.02], congenital malformations of heart and great artery (OR: 1.07; 95%CI: 1.00 to 1.14, P = 0.04), haemangioma and lymphangioma (OR: 1.12; 95%CI: 1.03 to 1.21, P = 0.01), and haemangioma (OR: 1.12; 95%CI: 1.03 to 1.22, P = 0.01). Genetically-predicted MDD was associated with reduced risk of varicose veins (OR: 0.87; 95%CI: 0.78 to 0.96, P = 0.01), giant cell arteritis (OR: 0.59; 95%CI: 0.36 to 0.97, P = 0.04), haemangioma and lymphangioma (OR: 0.71; 95%CI: 0.52 to 0.97, P = 0.03), and haemangioma (OR: 0.70; 95%CI: 0.50 to 0.98, P = 0.04), with an increased risk of pulmonary embolism (OR: 1.21; 95%CI: 1.02 to 1.45, P = 0.03). No significant association was observed for AD or BD. Evidence from bidirectional MR did not support reverse causality. Conclusion This study report evidence in support of potential causal associations of schizophrenia and MDD with several APVD. Further studies are needed to validate the findings and investigate potential mechanisms.