Longitudinal analysis of genetic and environmental interplay in human metabolic profiles and the implication for metabolic health

作者：Jing Wang, Alberto Zenere, Xingyue Wang, Göran Bergström, Fredrik Edfors, Mathias Uhlén, Wen Zhong · 发表于：Genome Medicine · 年份：2025 · DOI：10.1186/s13073-025-01492-y · 被引用次数：7 · 研究领域：Metabolomics and Mass Spectrometry Studies、Nutrition, Genetics, and Disease、Health, Environment, Cognitive Aging

BACKGROUND: Understanding how genetics and environmental factors shape human metabolic profiles is crucial for advancing metabolic health. Variability in metabolic profiles, influenced by genetic makeup, lifestyle, and environmental exposures, plays a critical role in disease susceptibility and progression. METHODS: We conducted a two-year longitudinal study involving 101 clinically healthy individuals aged 50 to 65, integrating genomics, metabolomics, lipidomics, proteomics, clinical measurements, and lifestyle questionnaire data from repeat sampling. We evaluated the influence of both external and internal factors, including genetic predispositions, lifestyle factors, and physiological conditions, on individual metabolic profiles. Additionally, we developed an integrative metabolite-protein network to analyze protein-metabolite associations under both genetic and environmental regulations. RESULTS: Our findings highlighted the significant role of genetics in determining metabolic variability, identifying 22 plasma metabolites as genetically predetermined. Environmental factors such as seasonal variation, weight management, smoking, and stress also significantly influenced metabolite levels. The integrative metabolite-protein network comprised 5,649 significant protein-metabolite pairs and identified 87 causal metabolite-protein associations under genetic regulation, validated by showing a high replication rate in an independent cohort. This network revealed stable and uniqu...