Mapping the plasma metabolome to human health and disease in 274,241 adults
Jia You, Xi-Han Cui, Yilin Chen, Yixuan Wang, Haiyun Li, Yi‐Xuan Qiang, Ji-Yun Cheng, Yue‐Ting Deng, Yu Guo, Peng Ren, Yi Zhang, Yu He, Xiaoyu He, Shi-Dong Chen, Yaru Zhang, Yuyuan Huang, Ying Mao, Jianfeng Feng, Wei Cheng, Jin‐Tai Yu
Abstract
A systematic characterization of metabolic profiles in human health and disease enhances precision medicine. Here we present a comprehensive human metabolome-phenome atlas, using data from 274,241 UK Biobank participants with nuclear magnetic resonance metabolic measures. This atlas links 313 plasma metabolites to 1,386 diseases and 3,142 traits, with participants being prospectively followed for a median of 14.9 years. This atlas uncovered 52,836 metabolite-disease and 73,639 metabolite-trait associations, where the ratio of cholesterol to total lipids in large low-density lipoprotein percentage was found as the metabolite associated with the highest number (n = 526) of diseases. In addition, we found that more than half (57.5%) of metabolites showed statistical variations from healthy individuals over a decade before disease onset. Combined with demographics, the machine-learning-based metabolic risk score signified the top 30 (around 10%) metabolites as biomarkers, yielding favourable classification performance (area under the curve > 0.8) for 94 prevalent and 81 incident diseases. Finally, Mendelian randomization analyses provided support for causal relationships of 454 metabolite-disease pairs, among which 402 exhibited shared genetic determinants. Additional insights can be gleaned via an accessible interactive resource ( https://metabolome-phenome-atlas.com/ ).