Mendelian randomization of autoimmune hepatitis and cardiovascular diseases

Abstract

Previous studies have shown that autoimmune hepatitis (AIH) is associated with cardiovascular diseases (CVD), but the potential causal relationship between genetic susceptibility to AIH and CVD risk is unknown. This study systematically investigated the potential association between genetically determined AIH and the risk of CVD. The analysis was conducted by genome-wide association studies (GWAS), considering AIH as the exposure and cardiovascular disease as the endpoint. Mendelian randomization (MR) analysis was performed using inverse variance weighting (IVW) as the primary method. Additionally, a series of pleiotropy, heterogeneity test and sensitivity analyses were conducted to verify the reliability of the results.MR analysis showed that genetic susceptibility to AIH was associated with a higher risk of atrial fibrillation [OR = 1.01, 95 % CI (1.00–1.02), p = 0.025]. However, it was found that negative relationship with dilated cardiomyopathy [OR = 0.91, 95 %CI (0.87–0.95), p < 0.001], coronary heart disease [OR = 0.94, 95 %CI (0.91–0.96), p < 0.001], hypertension [OR = 0.97, 95 % CI (0.96–0.99), p < 0.001], ischemic stroke [OR = 0.97, 95 % CI (0.96–0.99), p = 0.009], and intracerebral hemorrhage [OR = 0.95, 95 % CI (0.91–0.99), p = 0.013]. Sensitivity analysis has shown no evidence of horizontal pleiotropy or heterogeneity. Although some ORs are statistically significant, their clinical significance may be limited. In conclusion, our MR study explored the causal role of AIH in the etiology of CVD, which would help improve our understanding of the basic disease mechanisms of AIH and provide comprehensive CVD assessment and treatment for AIH patients.