Mendelian randomized data mining for genome-wide association studies suggests a causal relationship between cathepsins and cardiovascular diseases

Cardiovascular diseases (CVDs) have long been a serious threat to human health and longevity. Cathepsins are involved in a variety of human physiological processes and have a significant impact on the function of the cardiovascular system. Studies have demonstrated an association between cathepsins and cardiovascular disease, and we further investigated whether there are risk and protective factors between various cathepsins and cardiovascular diseases by using a Mendelian randomization approach. This study included 9 cathepsins (B, E, F, G, H, O, S, Z, L2) as exposures, 9 cardiovascular diseases (coronary atherosclerosis, essential hypertension, arrhythmia, angina pectoris, aplastic anemia, heart failure, stroke, malignant lymphoma, and myocardial infarction), and 3 anthropometric indices (Platelet count, diastolic blood pressure, systolic blood pressure) as outcomes. For the Mendelian randomization results, the inverse variance weighting (IVW) method was mainly used, and in order to ensure the accuracy of the results, we carried out the tests of multiplicity and heterogeneity, and the sensitivity analysis using the leave-one-out method. According to the results of MR analysis, cathepsin E is a risk factor for Coronary atherosclerosis (OR=1.0033, 95%CI=1.001-1.0056, P=0.0051) and Myocardial infarction (OR=1.0553, 95%CI=1.0131-1.0993, P=0.0097) and a protective factor for Platelet count (OR=0.9836, 95%CI=0.9728-0.9944, P=0.0031). Cathepsin Z is a risk factor for Essential hypertension (OR=1.0005, 95%CI=1.0000-1.0009, P=0.0439). Cathepsin L2 is a protective factor in chronic heart failure (OR=0.9255, 95%CI=0.8768-0.9769, P=0.005). Cathepsin B is a protective factor for systolic blood pressure (OR=0.801, 95%CI=0.6490-0.9885, P=0.0387).