Viet Susan Marie, Dellarco Michael, Chen Edith, McDade Thomas, Faustman Elaine, Brachvogel Sean, Smith Marissa, Wright Rosalind
Westat, Rockville, MD, United States.
Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, United States.
Front Pediatr. 2021 Apr 29;9:629487. doi: 10.3389/fped.2021.629487. eCollection 2021.
An important step toward understanding the relationship between the environment and child health and development is the comprehensive cataloging of external environmental factors that may modify health and development over the life course. Our understanding of the environmental influences on health is growing increasingly complex. Significant key questions exist as to what genes, environment, and life stage mean to defining normal variations and altered developmental trajectories throughout the life course and also across generations. With the rapid advances in genetic technology came large-scale genomic studies to search for the genetic etiology of complex diseases. While genome-wide association studies (GWAS) have revealed genetic factors and networks that advance our understanding to some extent, it is increasingly recognized that disease causation is largely non-genetic and reflects interactions between an individual's genetic susceptibility and his or her environment. Thus, the full promise of the human genome project to prevent or treat disease and promote good health arguably depends on a commitment to understanding the interactions between our environment and our genetic makeup and requires a design with prospective environmental data collection that considers critical windows of susceptibility that likely correspond to the expression of specific genes and gene pathways. Unlike the genome, which is static, relevant exposures as well as our response to exposures, change over time. This has fostered the complementary concept of the exposome ideally defined as the measure of all exposures of an individual over a lifetime and how those exposures relate to health. The exposome framework considers multiple external exposures (e.g., chemical, social) and behaviors that may modify exposures (e.g., diet), as well as consequences of environmental exposures indexed via biomarkers of physiological response or measures of behavioral response throughout the lifespan. The exposome concept can be applied in prospective developmental studies such as the National Children's Study (NCS) with the practical understanding that even a partial characterization will bring major advances to health. Lessons learned from the NCS provide an important opportunity to inform future studies that can leverage these evolving paradigms in elucidating the role of environment on health across the life course.
朝着理解环境与儿童健康及发育之间关系迈出的重要一步，是全面梳理可能在生命历程中影响健康和发育的外部环境因素。我们对环境对健康影响的理解正变得日益复杂。关于基因、环境和生命阶段在定义整个生命历程乃至跨代的正常变异和改变的发育轨迹方面意味着什么，存在重大关键问题。随着基因技术的迅速发展，出现了大规模基因组研究以探寻复杂疾病的遗传病因。虽然全基因组关联研究（GWAS）揭示了在一定程度上推进我们理解的遗传因素和网络，但人们越来越认识到疾病成因很大程度上是非遗传的，反映了个体遗传易感性与其环境之间的相互作用。因此，人类基因组计划在预防或治疗疾病以及促进健康方面的全部潜力，可以说取决于致力于理解我们的环境与基因构成之间的相互作用，并且需要一种设计，即前瞻性地收集环境数据，考虑可能与特定基因和基因途径表达相对应的关键易感性窗口。与静态的基因组不同，相关暴露以及我们对暴露的反应会随时间变化。这催生了互补的暴露组概念，理想情况下，暴露组被定义为个体一生中所有暴露的度量以及这些暴露与健康的关系。暴露组框架考虑多种外部暴露（如化学、社会方面的）以及可能改变暴露的行为（如饮食），还有通过生理反应生物标志物或整个生命周期行为反应测量指标来索引的环境暴露后果。暴露组概念可应用于前瞻性发育研究，如国家儿童研究（NCS），实际情况是，即使是部分特征描述也将给健康带来重大进展。从NCS中吸取的经验教训为指导未来研究提供了重要机会，这些研究可以利用这些不断发展的范式来阐明环境在整个生命历程中对健康的作用。
