Xin Liu1, Lin Shi2, Xiaoshuang Dai3, Huangtao Chen4, Chenglin Zhang4, Pei Wang4, Qian Wu5, Lingxia Zeng5, Hong Yan6. 1. Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, 710061, Xi'an, Shaanxi, China. Electronic address: xinliu@xjtu.edu.cn. 2. Department of Biology and Biological Engineering, Food and Nutrition Science, Chalmers University of Technology, Gothenburg, SE-412 96, Sweden; School of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi' an, 710062, China. 3. BGI Institute of Applied Agriculture, BGI-Agro, Shenzhen, 518083, PR China. Electronic address: daixiaoshuang@genomics.cn. 4. Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, 710061, Xi'an, Shaanxi, China. 5. Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, 710061, Xi'an, Shaanxi, China. 6. Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, 710061, Xi'an, Shaanxi, China; Nutrition and Food Safety Engineering Research Center of Shaanxi Province, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, 76 West Yanta Road, 710061, Xi'an, Shaanxi, China.
Abstract
BACKGROUND AND AIMS: Increased intake of whole/coarse grains was associated with improved blood pressure control, but concurrent metabolism alterations are less clear. We sought to identify metabolomic profiles of blood pressure, and to explore their mediation effects on the coarse grain intake-blood pressure association among young adults free of hypertension. METHODS AND RESULTS: Plasma metabolome of 86 participants from the Carbohydrate Alternatives and Metabolic Phenotypes study was characterized by untargeted lipidomics and metabolomics using liquid chromatography-high-resolution mass spectrometry. We identified 24 and 117 metabolites associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively, using random forest modeling and partial correlation analysis. Moreover, metabolite panels for highly specific prediction of blood pressure (8 metabolites for SBP and 11 metabolites for DBP) were determined using ten-fold cross-validated ridge regression (R2 ≥ 0.70). We also observed an inverse association between metabolite panel of SBP (β ± SE = -0.02 ± 0.01, P = 0.04) or DBP (β ± SE = -0.03 ± 0.01, P = 0.02) and coarse grain intake. Furthermore, we observed significant mediating effects of metabolites, in particular, sphingolipid ceramides, on the association between coarse grain exposure and blood pressure using both bias-corrected bootstrap tests and high-dimensional mediation analysis adapted for large-scale and high-throughput omics data. CONCLUSIONS: We identified metabolomic profiles specifically associated with blood pressure in young Chinese adults without diagnosed hypertension. The inverse association between coarse grain intake and blood pressure may be mediated by sphingolipid metabolites.
BACKGROUND AND AIMS: Increased intake of whole/coarse grains was associated with improved blood pressure control, but concurrent metabolism alterations are less clear. We sought to identify metabolomic profiles of blood pressure, and to explore their mediation effects on the coarse grain intake-blood pressure association among young adults free of hypertension. METHODS AND RESULTS: Plasma metabolome of 86 participants from the Carbohydrate Alternatives and Metabolic Phenotypes study was characterized by untargeted lipidomics and metabolomics using liquid chromatography-high-resolution mass spectrometry. We identified 24 and 117 metabolites associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively, using random forest modeling and partial correlation analysis. Moreover, metabolite panels for highly specific prediction of blood pressure (8 metabolites for SBP and 11 metabolites for DBP) were determined using ten-fold cross-validated ridge regression (R2 ≥ 0.70). We also observed an inverse association between metabolite panel of SBP (β ± SE = -0.02 ± 0.01, P = 0.04) or DBP (β ± SE = -0.03 ± 0.01, P = 0.02) and coarse grain intake. Furthermore, we observed significant mediating effects of metabolites, in particular, sphingolipidceramides, on the association between coarse grain exposure and blood pressure using both bias-corrected bootstrap tests and high-dimensional mediation analysis adapted for large-scale and high-throughput omics data. CONCLUSIONS: We identified metabolomic profiles specifically associated with blood pressure in young Chinese adults without diagnosed hypertension. The inverse association between coarse grain intake and blood pressure may be mediated by sphingolipid metabolites.