AUTHOR=Wang Han , Luo Qiang , Ding Xunshi , Chen Lifang , Zhang Zheng 

TITLE=Trimethylamine N-oxide and its precursors in relation to blood pressure: A mendelian randomization study

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.922441

DOI=10.3389/fcvm.2022.922441

ISSN=2297-055X

ABSTRACT=Abstract 
Objective: Previous studies have demonstrated that trimethylamine N-oxide (TMAO) and its precursors, including choline, betaine, and carnitine, are closely associated with blood pressure (BP) changes. Nevertheless, with the limitation of reverse causality and confounder in observational studies, such a relationship remains unclear. We aimed to assess the causal relationship of TMAO and its precursors with BP by the Mendelian Randomization (MR) approach. 
Method: Summary statistics for TMAO and its precursors and BP were extracted from genome-wide association studies (GWAS). Inverse variance weighted (IVW), MR Egger regression, Maximum likelihood, Weighted median, and MR pleiotropy residual sum and outlier test (MR-PRESSO) were used in this MR analysis. 
Results: A total of 160 independent SNP loci were associated with TMAO and three precursors, including 58 associated with TMAO, 29 associated with choline, 44 associated with betaine, and 29 associated with carnitine, were selected. MR results suggested that for each 1 unit increase in TMAO, the risk of systolic BP increased by 7.1% (OR =1.071, 95%CI 1.010 to 1.136, p=0.020). Additionally, our findings also indicated that for each 1 unit increase in carnitine, the risk of systolic BP increased by 7.6% (OR =1.076, 95%CI 1.003 to 1.156, p=0.039). This result was also confirmed by sensitivity analysis methods such as Maximum likelihood, MR-PRESSO, and Weighted median. No effects of betaine or choline on systolic or diastolic BP were observed in the present study.
Conclusion: Our study provides evidence of a causal relationship of TMAO and its precursors with BP, suggesting that mediating the generation of TMAO would be beneficial for lowering BP.