人类代谢谱中基因与环境相互作用的纵向分析及其对代谢健康的影响。
Longitudinal analysis of genetic and environmental interplay in human metabolic profiles and the implication for metabolic health.
作者信息
Wang Jing, Zenere Alberto, Wang Xingyue, Bergström Göran, Edfors Fredrik, Uhlén Mathias, Zhong Wen
机构信息
Department of Biomedical and Clinical Sciences (BKV), Linköping University, SE-581 83, Linköping, Sweden.
Science for Life Laboratory, Linköping University, Linköping, Sweden.
出版信息
Genome Med. 2025 Jun 17;17(1):68. doi: 10.1186/s13073-025-01492-y.
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 unique protein-metabolite profiles for each individual, emphasizing metabolic individuality. Notably, our results demonstrated the importance of plasma proteins in capturing individualized metabolic variabilities. Key proteins related to individual metabolic profiles were identified and validated in the UK Biobank, showing great potential for metabolic risk assessment.
CONCLUSIONS
Our study provides longitudinal insights into how genetic and environmental factors shape human metabolic profiles, revealing unique and stable individual metabolic profiles. Plasma proteins emerged as key indicators for capturing the variability in human metabolism and assessing metabolic risks. These findings offer valuable tools for personalized medicine and the development of diagnostics for metabolic diseases.
背景
了解遗传和环境因素如何塑造人类代谢谱对于促进代谢健康至关重要。受遗传构成、生活方式和环境暴露影响的代谢谱变异性在疾病易感性和进展中起着关键作用。
方法
我们对101名年龄在50至65岁之间的临床健康个体进行了为期两年的纵向研究，整合了来自重复采样的基因组学、代谢组学、脂质组学、蛋白质组学、临床测量和生活方式问卷数据。我们评估了包括遗传易感性、生活方式因素和生理状况在内的外部和内部因素对个体代谢谱的影响。此外，我们构建了一个整合的代谢物 - 蛋白质网络，以分析遗传和环境调控下的蛋白质 - 代谢物关联。
结果
我们的研究结果突出了遗传在决定代谢变异性方面的重要作用，确定了22种血浆代谢物为遗传预先决定的。季节变化、体重管理、吸烟和压力等环境因素也显著影响代谢物水平。整合的代谢物 - 蛋白质网络包含5649对显著的蛋白质 - 代谢物对，并在遗传调控下鉴定出87种因果代谢物 - 蛋白质关联，在独立队列中显示出高重复率从而得到验证。该网络揭示了每个个体稳定且独特的蛋白质 - 代谢物谱，强调了代谢个体性。值得注意的是，我们的结果证明了血浆蛋白在捕捉个体代谢变异性方面的重要性。与个体代谢谱相关的关键蛋白在英国生物银行中得到鉴定和验证，显示出在代谢风险评估方面的巨大潜力。
结论
我们的研究提供了关于遗传和环境因素如何塑造人类代谢谱的纵向见解，揭示了独特且稳定的个体代谢谱。血浆蛋白成为捕捉人类代谢变异性和评估代谢风险的关键指标。这些发现为个性化医疗和代谢疾病诊断方法的开发提供了有价值的工具。
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