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

IF 10.4 1区 生物学 Q1 GENETICS & HEREDITY
Jing Wang, Alberto Zenere, Xingyue Wang, Göran Bergström, Fredrik Edfors, Mathias Uhlén, Wen Zhong
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引用次数: 0

Abstract

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.

遗传和环境在人类代谢谱中的相互作用的纵向分析及其对代谢健康的影响。
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。受基因组成、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,整合了基因组学、代谢组学、脂质组学、蛋白质组学、临床测量和重复抽样的生活方式问卷数据。我们评估了外部和内部因素对个体代谢谱的影响,包括遗传易感性、生活方式因素和生理条件。此外,我们开发了一个综合代谢物-蛋白质网络来分析遗传和环境调节下蛋白质-代谢物的关联。结果:我们的研究结果强调了遗传在决定代谢变异性中的重要作用,确定了22种血浆代谢物是遗传预定的。环境因素如季节变化、体重管理、吸烟和压力也显著影响代谢物水平。综合代谢物-蛋白质网络包括5649对重要的蛋白质-代谢物对,并在遗传调控下确定了87种代谢物-蛋白质因果关联,在独立队列中显示出高复制率。该网络揭示了每个个体稳定和独特的蛋白质代谢物谱,强调了代谢个性。值得注意的是,我们的结果证明了血浆蛋白在捕获个体化代谢变异方面的重要性。与个体代谢谱相关的关键蛋白在UK Biobank中被鉴定和验证,显示出代谢风险评估的巨大潜力。结论:我们的研究提供了遗传和环境因素如何塑造人类代谢谱的纵向见解,揭示了独特而稳定的个体代谢谱。血浆蛋白成为捕捉人体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性疾病诊断的发展提供了有价值的工具。
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来源期刊
Genome Medicine
Genome Medicine GENETICS & HEREDITY-
CiteScore
20.80
自引率
0.80%
发文量
128
审稿时长
6-12 weeks
期刊介绍: Genome Medicine is an open access journal that publishes outstanding research applying genetics, genomics, and multi-omics to understand, diagnose, and treat disease. Bridging basic science and clinical research, it covers areas such as cancer genomics, immuno-oncology, immunogenomics, infectious disease, microbiome, neurogenomics, systems medicine, clinical genomics, gene therapies, precision medicine, and clinical trials. The journal publishes original research, methods, software, and reviews to serve authors and promote broad interest and importance in the field.
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