Variation of DNA Methylation in Newborns Associated with Exhaled Carbon Monoxide during Pregnancy

Abstract

Fetal exposure to tobacco smoke is an adverse risk factor for newborns. A plausible mechanism of how this exposure may negatively impact long term health is differential methylation of deoxyribonucleic acid (DNAm) and its relation to birth weight. We examined whether self-reported gestational smoking status and maternal exhaled carbon monoxide (eCO) during early pregnancy were associated with methylation of cytosine by guanines (CpG) sites that themselves predicted birth weight. We focused first on CpGs associated with maternal smoking, and secondly, among these, on CpGs related to birth weight found in another cohort. Then in 94 newborns from the Breathing for Life Trial (BLT) DNAm levels in cord blood were determined using Infinium Methylation EPIC BeadChip measuring >850K CpGs. We regressed CpGs on eCO and tested via mediation analysis whether CpGs link eCO to birth weight. Nine smoking related CpG sites were significantly associated with birth weight. Among these nine CpGs the methylation of cg02264407 on the LMO7 gene was statistically significant and linked with eCO measurements. eCO greater than six ppm showed a 2.3% decrease in infant DNAm (p = 0.035) on the LMO7 gene. A 1% decrease in methylation at this site resulted in decreased birth weight by 44.8 g (p = 0.003). None of the nine CpGs tested was associated with self-reported smoking. This is the first study to report potential mediation of DNA methylation, linking eCO measurements during early pregnancy with birth weight.

Polymorphisms in Glutathione S-Transferase (GST) Genes Modify the Effect of Exposure to Maternal Smoking Metabolites in Pregnancy and Offspring DNA Methylation

“…The CpG site cg12160087 is associated with the Coiled-coil domain containing 64 ( CCDC64 ), a protein-coding gene involved in cellular transport and nervous system development [ 52 ]. DNAm at cg12160087 has been positively associated with offspring birth weight [ 53 ]. Previous research shows that genetic polymorphisms of the GSTM3 gene affect lung function (FEV1 and FVC) by interacting with MSP [ 38 ].…”

Waterpipe and cigarette epigenome analysis reveals markers implicated in addiction and smoking type inference

“…Eleven studies were retrieved: four on cord blood ( Howe et al, 2019 , Bergens et al, 2019 , De Queiroz Andrade et al, 2021 , Danielewicz et al, 2021 ), one on saliva and peripheral blood leukocytes ( Barcelona et al, 2019 ), one on leukocyte subtypes ( Wang et al, 2023 ), one on bronchoalveolar cells ( Ringh et al, 2019 ), one on nucleus accumbens brain cells ( Markunas et al, 2021 ), two on peripheral blood ( Christiansen et al, 2021 , Domingo-Relloso et al, 2020 ), and one study was irrelevant ( Osborne et al, 2020 ). The two studies involving 850 K profiling on peripheral blood ( Christiansen et al, 2021 , Domingo-Relloso et al, 2020 ) are not yet reported in the EWAS data hub, and, among them, the study by Christiansen et al ( Christiansen et al, 2021 ) was used as our 850 K reference because it conducted a meta -analysis of multiple cohorts, and already covered the second study by Domingo-Relloso et al .…”