Body mass index increases uric acid in East Asian population: a Mendelian randomization study

Background: Previous observational and Mendelian randomization studies suggested that the increase in serum uric acid causes adiposity, not vice versa. However, most findings came from data on European ancestry. Among East Asian populations, both directions in the causal relationship between adiposity and uric acid have been suggested by observational studies and a few MR studies. In this study, we tested the hypothesis of the causal effect of body mass index (BMI) on serum uric acid in East Asian populations.Methods: Summary statistics from two large, publicly available biobanks from South Korea (72,299 participants in the Korean Genome and Epidemiology Study) and Japan (158,284 participants in the Biobank Japan) were utilized to conduct a two-sample Mendelian randomization study.Results: We found that genetically determined BMI has a positive causal effect on serum uric acid in various Mendelian randomization methods (inverse-variance weighted: B [95% CI] = 0.029 [-0.006, 0.065]; simple mode: a [95% CI] = 0.053 [0.009, 0.097]); weighted mode: c [95% CI] = 0.036 [0.005, 0.067]); weighted median: k [95% CI] = 0.042 [0.019, 0.065]). Multiple robustness checks such as a funnel plot, leave-one-out analyses, and an MR-Egger regression did not suggest directional horizontal pleiotropy. Conclusions: Genetically determined BMI increases serum uric acid in East Asian populations. Our findings from the South Korean and Japanese populations are consistent with previous observations in the European population.