暴露物-现象关联的架构
Chirag J Patel1, John Pa Ioannidis2,3, Arjun K Manrai1
1Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
medRxiv : the preprint server for health sciences
|July 15, 2025
概括
环境暴露对健康产生重大影响,影响我们身体的发育和功能. 这项研究表明,环境因素的结合解释了健康变异和数百万个遗传变异一样多.
科学领域:
- 环境健康科学 环境健康科学
- 基因组学和精准医学精准医学
- 计算生物学 计算生物学
背景情况:
- 非遗传性暴露 (营养,生活方式,污染物) 显著导致人类表型变异.
- 目前的研究经常检查有限的暴露和现象型,导致对暴露-现象关系的理解分散.
- 需要一种系统的方法来全面量化暴露基对临床相关表型的广泛影响.
研究的目的:
- 开发一种资源,用于对曝光体在健康中的作用进行基准测试.
- 系统地测试各种环境暴露和临床表型之间的关联.
- 量化多次暴露对表型变异的累积影响.
主要方法:
- 使用了来自国家健康和营养检查调查 (NHANES) 的数据.
- 编目了619种不同的暴露和278种表型.
- 进行了表型-暴露-广泛的关联研究 (P-ExWAS) 以系统地测试约119,000个关联.
主要成果:
- 鉴定了5,661个 (5%) Bonferroni暴露和表型之间的显著关联,其中40%在独立样本中复制.
- 个人暴露解释了表型变异的中位数为0.5%.
- 20个同时出现的暴露因子解释了平均3.5%的变异,相当于100万个遗传变异.
结论:
- 暴露体在表型变异中发挥着实质性的作用,其大小与遗传影响相当.
- 一个全面的,多次暴露的方法对于理解健康和疾病至关重要.
- 开发的exposome-phenome图谱为未来的研究和临床应用提供了宝贵的资源.
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