Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, Maryland.
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana.
J Hypertens. 2020 Jul;38(7):1302-1311. doi: 10.1097/HJH.0000000000002363.
To identify novel and confirm previously reported metabolites associated with SBP, DBP, and hypertension in a biracial sample of Bogalusa Heart Study (BHS) participants.
We employed untargeted, ultra-high performance liquid chromatography tandem mass spectroscopy metabolomics profiling among 1249 BHS participants (427 African-Americans and 822 whites) with BP and covariable data collected during the 2013 to 2016 visit cycle. A total of 1202 metabolites were tested for associations with continuous and binary BP phenotypes using multiple linear and logistic regression models, respectively, in overall and race-stratified analyses.
A total of 24 novel metabolites robustly associated with BP, achieving Bonferroni-corrected P less than 4.16 × 10 in the overall analysis and consistent effect sizes across race groups. The identified metabolites included three amino acid and nucleotide metabolites from histidine, pyrimidine, or tryptophan metabolism sub-pathways, seven cofactor and vitamin or xenobiotic metabolites from the ascorbate and aldarate metabolism, bacterial/fungal, chemical, and food component sub-pathways, 10 lipid metabolites from the eicosanoid, phosphatidylcholine, phosphatidylethanolamine, and sphingolipid metabolism sub-pathways, and four still unnamed metabolites. Six previously described metabolites were robustly confirmed by our study (Bonferroni-corrected P < 4.95 × 10 and consistent effect directions across studies). Furthermore, previously reported metabolites for SBP, DBP, and hypertension demonstrated 5.92-fold, 4.77-fold, and 4.54-fold enrichment for nominally significant signals in the BHS (P = 3.08 × 10, 5.93 × 10, and 2.30 × 10, respectively).
In aggregate, our study provides new information about potential molecular mechanisms underlying BP regulation. We also demonstrate reproducibility of findings across studies despite differences in study populations and metabolite profiling methods.
在博加卢萨心脏研究（BHS）参与者的一个黑白裔混合样本中，鉴定与 SBP、DBP 和高血压相关的新的和已报道的代谢物。
我们在 2013 年至 2016 年的访问周期中，对 1249 名 BHS 参与者（427 名非裔美国人和 822 名白人）的血压和协变量数据进行了非靶向、超高液相色谱串联质谱代谢组学分析。使用多元线性和逻辑回归模型，分别在总体和种族分层分析中，对 1202 种代谢物与连续和二分类 BP 表型的相关性进行了测试。
共有 24 种新的代谢物与 BP 显著相关，在总体分析中达到了 Bonferroni 校正的 P 值小于 4.16×10，并且在种族组之间具有一致的效应大小。鉴定出的代谢物包括组氨酸、嘧啶或色氨酸代谢途径的三种氨基酸和核苷酸代谢物、抗坏血酸和醛酸代谢途径以及细菌/真菌、化学和食物成分途径的七种辅因子和维生素或外源性代谢物、二十烷酸、磷脂酰胆碱、磷脂酰乙醇胺和鞘脂代谢途径的 10 种脂质代谢物，以及四种仍未命名的代谢物。本研究还稳健地证实了六种以前描述过的代谢物（Bonferroni 校正的 P 值小于 4.95×10，且研究间的效应方向一致）。此外，SBP、DBP 和高血压的以前报道的代谢物在 BHS 中表现出显著信号的 5.92 倍、4.77 倍和 4.54 倍富集（P 值分别为 3.08×10、5.93×10 和 2.30×10）。
总的来说，本研究提供了关于血压调节潜在分子机制的新信息。尽管研究人群和代谢物分析方法存在差异，但我们也证明了研究结果的可重复性。
