Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Canada.
Peter Boris Centre for Addictions Research, St. Joseph's Healthcare Hamilton, Hamilton, Canada.
Elife. 2024 Aug 14;13:RP93260. doi: 10.7554/eLife.93260.
Maternal smoking has been linked to adverse health outcomes in newborns but the extent to which it impacts newborn health has not been quantified through an aggregated cord blood DNA methylation (DNAm) score. Here, we examine the feasibility of using cord blood DNAm scores leveraging large external studies as discovery samples to capture the epigenetic signature of maternal smoking and its influence on newborns in White European and South Asian populations.
We first examined the association between individual CpGs and cigarette smoking during pregnancy, and smoking exposure in two White European birth cohorts (n=744). Leveraging established CpGs for maternal smoking, we constructed a cord blood epigenetic score of maternal smoking that was validated in one of the European-origin cohorts (n=347). This score was then tested for association with smoking status, secondary smoking exposure during pregnancy, and health outcomes in offspring measured after birth in an independent White European (n=397) and a South Asian birth cohort (n=504).
Several previously reported genes for maternal smoking were supported, with the strongest and most consistent association signal from the gene (6 CpGs with p<5 × 10). The epigenetic maternal smoking score was strongly associated with smoking status during pregnancy (OR = 1.09 [1.07, 1.10], p=5.5 × 10) and more hours of self-reported smoking exposure per week (1.93 [1.27, 2.58], p=7.8 × 10) in White Europeans. However, it was not associated with self-reported exposure (p>0.05) among South Asians, likely due to a lack of smoking in this group. The same score was consistently associated with a smaller birth size (-0.37±0.12 cm, p=0.0023) in the South Asian cohort and a lower birth weight (-0.043±0.013 kg, p=0.0011) in the combined cohorts.
This cord blood epigenetic score can help identify babies exposed to maternal smoking and assess its long-term impact on growth. Notably, these results indicate a consistent association between the DNAm signature of maternal smoking and a small body size and low birth weight in newborns, in both White European mothers who exhibited some amount of smoking and in South Asian mothers who themselves were not active smokers.
This study was funded by the Canadian Institutes of Health Research Metabolomics Team Grant: MWG-146332.
母体吸烟与新生儿不良健康结果有关，但通过聚合脐带血 DNA 甲基化（DNAm）评分来量化其对新生儿健康的影响程度尚未得到量化。在这里，我们利用大型外部研究作为发现样本，检查使用脐带血 DNAm 评分来捕获母体吸烟的表观遗传特征及其对白种欧洲人和南亚人群中新生儿的影响的可行性。
我们首先在两个白种欧洲出生队列（n=744）中检查了个体 CpG 与怀孕期间吸烟和吸烟暴露之间的关联。利用已建立的用于母体吸烟的 CpG，我们构建了一个脐带血母体吸烟表观遗传评分，该评分在其中一个欧洲起源队列（n=347）中得到验证。然后，在一个独立的白种欧洲人（n=397）和南亚出生队列（n=504）中，测试该评分与吸烟状况、怀孕期间的二次吸烟暴露以及出生后测量的后代健康结果之间的关联。
支持了几个先前报道的母体吸烟基因，其中最强和最一致的关联信号来自基因（6 个 CpG，p<5 × 10）。母体吸烟的表观遗传评分与怀孕期间的吸烟状况（OR=1.09[1.07，1.10]，p=5.5 × 10）和每周自我报告的吸烟暴露时间（1.93[1.27，2.58]，p=7.8 × 10）呈强相关在白种欧洲人中。然而，它与南亚人中的自我报告暴露无关（p>0.05），这可能是由于该组中没有吸烟。在南亚人群中，同一评分与出生时的较小体型（-0.37±0.12 cm，p=0.0023）始终相关，在联合队列中与出生体重较低（-0.043±0.013 kg，p=0.0011）相关。
这种脐带血表观遗传评分可以帮助识别接触母体吸烟的婴儿，并评估其对生长的长期影响。值得注意的是，这些结果表明，在表现出一定量吸烟的白种欧洲母亲和本身不主动吸烟的南亚母亲中，母体吸烟的 DNAm 特征与新生儿的体型较小和出生体重较低之间存在一致的关联。
本研究由加拿大卫生研究院代谢组学团队资助：MWG-146332。
