Potential Mediators of Causal Associations of Circulating Triglycerides With Blood Pressure: Evidence From Genetic and Observational Data

Abstract

Background: Existing evidence indicates that elevated triglycerides may affect blood pressure, but the underlying mechanisms are not fully understood. Herein, we aim to identify the intermediaries of associations of triglyceride with systolic blood pressure and diastolic blood pressure using the Mendelian randomization (MR) framework. Methods: Triglyceride-associated single nucleotide polymorphisms were extracted and used to match phenotypes in PhenoScanner. From the broad spectrum of possible triglyceride-associated traits, potential mediators linking triglyceride to blood pressure were screened out by MR and MR-based mediation analysis. Moreover, cross-sectional observational data of 206 341 adults were used to validate the mediators identified at the genetic level. Results: Among the nearly 100 raw phenotypes matched by 313 triglyceride-associated single nucleotide polymorphisms, 39 traits were filtered and integrated into subsequent analysis. By further filtering using MR analysis, only pulse rate and lymphocyte count (LC) were identified as independent mediators. MR-based mediation analysis showed that genetically predicted LC could mediate 9.2% of the association of triglyceride with systolic blood pressure; genetically predicted pulse rate and LC could mediate 18.3% and 17.6% of the association of triglyceride with DBP, respectively. Observational data also support the mediating role of pulse rate and LC. Conclusions: The current findings highlighted the mediating role of pulse rate and LC on the causal pathway from triglyceride to blood pressure and may contribute to a better understanding of the pathogenic mechanism by which high triglyceride affects other cardiometabolic factors.