The causal role of elevated uric acid and waist circumference on the risk of metabolic syndrome components

Background/objectives Hyperuricemia has been found to cluster with multiple components of metabolic syndrome (MetS). It is unclear whether hyperuricemia is a downstream result of MetS or may play an upstream role in MetS development. Using the Mendelian randomization (MR) method, we examined the causal relationship between elevated uric acid and the various components of MetS with waist circumference as a positive control. Subjects/methods Data from 10k participants of Taiwan Biobank was used to carry out MR analysis with uric acid risk score (wGRS) and waist circumference wGRS as instrumental variables and components of MetS as the outcomes. Results We found that genetically increased serum uric acid corresponds to a significant increment of triglyceride (beta = 0.065, p < 0.0001), systolic blood pressure (beta = 1.047, p = 0.0005), diastolic blood pressure (beta = 0.857, p < 0.0001), and mean arterial pressure (beta = 0.920, p < 0.0001), but a significant reduction of high-density lipoprotein cholesterol (beta = -0.020, p = 0.0014). Uric acid wGRS was not associated with fasting serum glucose, HbA1C, waist circumference, or BMI. On the other hand, waist circumference was causally associated with all the components of MetS including uric acid. Conclusions Our MR investigation shows that uric acid increment may augment the risk of MetS through increasing blood pressure and triglyceride levels and lowering HDL-C value but not through accumulating fat or hyperglycemia. High waist circumference may be a causal agent for all the components of MetS including hyperuricemia.