Background and Aim: As the effects of anthropogenic climate change increase the frequency and severity of wildfires in arid regions, the impacts of prenatal wildfire smoke exposure (WFE) on prenatal health will become relevant to an increasing number of pregnant women. Prior investigations have found associations between WFE and pregnancy complications, and postulated DNA methylation as a potential contributing mechanism for this effect. This preliminary study will investigate the placental DNA methylation changes associated with prenatal WFE, and search for differential methylation patterns that could inform the relationship between prenatal WFE and adverse pregnancy outcomes. Methods: DNA was extracted from 136 unique placental samples (124 not exposed to 2008 CA wildfires during pregnancy, 12 exposed) associated with metadata on wildfire exposure as well as other traits of interest. DNA underwent bisulfite conversion and subsequent whole genome bisulfite sequencing to reveal placental methylome. Placental methylomes were used to perform comethylation network analysis via the Comethyl package, generating modules of correlated methylation patterns across samples. Comethylation modules were then tested for association with sample metadata, including wildfire exposure. Results: Four comethylation modules (darkorange, darkred, saddlebrown, and plum2) were associated (p<0.05) with prenatal WFE. Two of these modules (darkorange and plum2) were also associated with maternal weight gain or gestational diabetes, with these modules being enriched for genes implicated in endothelial, vascular, neuronal, and DNA repair pathways. The darkred comethylation module was also associated with child and paternal Hispanic ethnicity characteristics, with the module itself being enriched for genes involved in mitochondrial chain respiratory pathways. Conclusions: A significant association exists between prenatal WFE, placental DNA methylation, and maternal weight gain. Larger cohorts of WFE samples are required to bolster the associations identified in this discovery analysis. Keywords: wildfires, prenatal, methylation
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