ABSTRACT
Objective:To explore the causal associations of two blood pressure phenotype and four lipid fractions with type 2 diabetes mellitus(T2DM) in European and East Asian populations using Two-Sample Mendelian randomization analysis.Methods:Blood pressure phenotype, lipid fractions and T2DM genetic loci from two ethnics were matched and combined according to single nucleotide polymorphisms(SNPs) numbering. With SNPs closely related to the exposure phenotype as instrumental variables, the inverse variance weighting method was used to analyze the causal effects of blood pressure phenotype and lipid fractions on T2DM in different ethnic groups. The sensitivity analysis was conducted using MR-Egger regression model, Weighted Median method, MR-PRESSO, MR-robust Adjusted Profile Score, and leave-one-out method.Results:Among European populations, systolic blood pressure( OR=1.40, 95% CI 1.23-1.59, P<0.001) and diastolic blood pressure( OR =1.24, 95% CI 1.08-1.42, P=0.002)were associated with increased risk of T2DM while high density lipoprotein-cholesterol( OR=0.68, 95% CI 0.62-0.76, P<0.001) reduced the risk of T2DM. In East Asian ethnicity, elevated diastolic blood pressure( OR=0.75, 95% CI 0.59-0.95, P=0.007) reduced the risk of T2DM. Sensitivity analysis confirmed the results. Conclusion:There are differences in the effects of blood pressure phenotype and lipid composition on T2DM in different ethnic groups, which may be related to population heterogeneity and exposure sensitivity. It should be taken into consideration in extrapolation.