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Abstract: PO1777

High Level of Uromodulin Increases the Risk of Hypertension: A Mendelian Randomization Study

Session Information

Category: Hypertension and CVD

  • 1401 Hypertension and CVD: Epidemiology, Risk Factors, and Prevention

Authors

  • You, Ruilian, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
  • Chen, Lanlan, Jilin University, Changchun, Jilin, China
  • Xu, Lubin, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
  • Li, Haitao, Jilin University, Changchun, Jilin, China
  • Shi, Xiaoxiao, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
  • Zheng, Yali, Ningxia Medical University, Yinchuan, Ningxia, China
  • Chen, Limeng, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
Background

The association of uromodulin and hypertension was clinically observed, but not proved as a causal relationship. We conducted a two-sample Mendelian randomization analysis to investigate the causal relationship between uromodulin and blood pressure based on the public datasets.

Methods

We selected two SNPs for the uUMOD exposure from the Genome-Wide Association Studies (GWAS) meta-analysis study(N=10884) and sixteen SNPs for sUMOD based on the open studies in Pubmed(N=4147). Six summary level studies based on the UKbibank and ICBP served as outcomes with the sample of hypertension is 46188, a total sample size of SBP is 1194020, and the DBP is 1194025. We used the Wald ratio to estimate the causal effect of urinary uromodulin(uUMOD) and the inverse variance weighted (IVW) method to combine each SNP’s effect. Three methods (IVW, MR-Egger, and Weighted median) were used to access the causal effect of serum uromodulin(sUMOD) on blood pressure. We also adopted Cochran’s Q statistic to test the heterogeneity and MR-PRESSO to confirm the horizontal pleiotropy.

Results

MR analysis of the IVW method shows uromodulin could elevate blood pressure and enhance the risk of hypertension. Odds Ratios(OR) of the uUMOD to hypertension (ukb-b-14057 and ukb-b-14177) is 1.04(95% Confidence Interval (CI), 1.03-1.04),while in sUMOD is 1.01(95%CI 1.01-1.02). Both sUMOD and uUMOD can predict the elevation of the SBP and DBP. The effect sizes of the uUMOD to SBP are 1.100 and 0.028 in ieu-b-39 and ukb-b-20175 respectively. The causal relationship between uUMOD and DBP of the ieu-b-39 is 0.88(p-value=4.38E-06) and 0.05 of the ukb-b-7992(p-value=2.13E-10). The β coefficient of sUMOD IVW in ieu-b-38 is 0.371 and 0.011 in ukb-b-20175. For DBP in ieu-b-39 are β=0.313 (SE=0.050) and β=0.018 (SE=0.003)in ukb-b-7992.

Conclusion

Our results solidly indicated that high urinary and serum uromodulin level is a causal risk factor for hypertension.