Prenatal Exposure to Artificial Light at Night and the Offspring’s First 1000-Day Growth: A Prospective Metabolomic and Gene-Environment Interaction Study

Our previous exposome study suggested associations between prenatal exposure to artificial light at night (ALAN) and offspring weight and fat growth during the first 1000 days. This study aims to further explore the underlying biomechanism and modifying effects of maternal genetic regulators. Among 1944 mother-child pairs from the Shanghai Birth Cohort, meet-in-the-middle, mediation, and enrichment analyses were combined with the early pregnancy untargeted metabolome to explore potential biological links between prenatal ALAN exposure and early life growth. Maternal polygenetic risk scores (PRS) for glucose- and lipid-metabolism-related phenotypes were constructed and dichotomized (high/low) to examine gene-environment interactions. We identified 35 mediating metabolites between prenatal ALAN exposure and growth outcomes, which were enriched in neural signal transduction-related pathways and associated with the circadian rhythm. The effects of ALAN exposure on fetal and child growth were more pronounced among mothers with high PRS levels for fasting glucose, HbA1c, and triglycerides. To sum up, prenatal ALAN exposure may be associated with reduced weight and adiposity gains during the first 1000 days. These associations may be partly explained by disturbances in maternal circadian rhythms and appeared more pronounced among mothers with high genetic predispositions to glucose and triglyceride levels.本课题组此前的暴露组学（exposome）研究提示，产前夜间人工光照（artificial light at night, ALAN）暴露与子代在生命早期1000天内的体重及脂肪增长存在关联。本研究旨在进一步阐明其潜在生物学机制，并探究母体遗传调控因子的修饰效应。本研究纳入上海出生队列（Shanghai Birth Cohort）的1944对母婴对，联合中间相遇分析、中介分析与富集分析，并结合早孕未靶向代谢组数据，探索产前ALAN暴露与早期生命生长之间的潜在生物学联系。研究构建了针对糖脂代谢相关表型的母体多基因风险评分（polygenetic risk scores, PRS），并将其划分为高、低两个分组，以此检验基因-环境交互作用。本研究鉴定出35种可介导产前ALAN暴露与生长结局之间关联的代谢物，这些代谢物富集于神经信号转导相关通路，且与昼夜节律存在显著关联。ALAN暴露对胎儿及儿童生长的影响，在空腹血糖、糖化血红蛋白（HbA1c）及甘油三酯相关PRS较高的母亲群体中更为显著。综上，产前ALAN暴露可能与子代在生命早期1000天内的体重及脂肪增长幅度降低存在关联。此类关联可部分通过母体昼夜节律紊乱得到解释，且在糖脂代谢水平具有较高遗传易感性的母亲群体中表现得更为突出。