摘要
Abstract
Objective This study aimed to perform a bidirectional twosample Mendelian randomization(MR)analysis to eval-uate potential causal associations of plasma metabolites and metabolic pathways with hypertension,providing novel insights into the etiology and prevention and treatment of hypertension.Methods Summary statistics for 1 091 human plasma me-tabolites and 309 metabolite ratios were obtained from genomewide association study(GWAS)metaanalyses.Hypertension summary data were sourced from the FinnGen database.The causal inference was conducted bidirectionally using inversevar-iance weighted(IVW),MREgger,weighted median,simple mode,weighted mode,and coefficient ratio methods.Sensitiv-ity analyses included heterogeneity tests,MREgger intercept,MRPRESSO,and leaveoneout analysis.Metabolic pathway a-nalysis was performed using the networkbased MetaboAnalyst 6.0.Results A total of 126 potential associations were iden-tified.After false discovery rate(FDR)correction and sensitivity analyses,41 robust causal relationships remained,with no evidence of reverse causation of hypertension on 38 of those metabolites or metabolite ratios.Pathway analysis revealed nine key metabolic pathways potentially implicated in the development of hypertension.Conclusion Using largescale bidirection-al MR,potential plasma metabolites and metabolic pathways affecting the development of hypertension were found,and their causal associations were inferential.关键词
血浆代谢组/孟德尔随机化/高血压/谷胱甘肽代谢/氨基酸代谢Key words
Plasma metabolome/Mendelian randomization/Hypertension/Glutathione metabolism/Amino acid metabolism分类
医药卫生
