Abstract
Lead (Pb) exposure remains a major concern in the United States (US) and around the world, even following the removal of Pb from gasoline and other products. Environmental Pb exposures from aging infrastructure and housing stock are of particular concern to pregnant women, children, and other vulnerable populations. Exposures during sensitive periods of development are known to influence epigenetic modifications which are thought to be one mechanism of the Developmental Origins of Health and Disease (DOHaD) paradigm. To gain insights into early life Pb exposure-induced health risks, we leveraged neonatal dried bloodspots in a cohort of children from Michigan, US to examine associations between blood Pb levels and concomitant DNA methylation profiles (n = 96). DNA methylation analysis was conducted via the Infinium MethylationEPIC array and Pb levels were assessed via high resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). While at-birth Pb exposure levels were relatively low (average 0.78 µg/dL, maximum of 5.27 ug/dL), we identified associations between DNA methylation and Pb at 33 CpG sites, with the majority (82%) exhibiting reduced methylation with increasing Pb exposure (q < 0.2). Biological pathways related to development and neurological function were enriched amongst top differentially methylated genes by p-value. In addition to increases/decreases in methylation, we also demonstrate that Pb exposure is related to increased variability in DNA methylation at 16 CpG sites. More work is needed to assess the accuracy and precision of metals assessment using bloodspots, but this study highlights the utility of this unique resource to enhance environmental epigenetics research around the world.
Highlights
Even with recent reductions in lead (Pb) exposure [1], Pb toxicity and related health effects remain a concern in nearly every country around the world
This study utilized neonatal dried bloodspots that were archived by the State of Michigan and underwent different storage conditions and storage time depending on the participant recruitment group
In the site-specific analysis of 789,147 CpG sites, we identified a number of genes with differential methylation by levels of Pb exposure
Summary
Even with recent reductions in lead (Pb) exposure [1], Pb toxicity and related health effects remain a concern in nearly every country around the world. Early life exposure can occur in utero via placental transfer, in infancy through breast milk, and directly from the drinking water and other sources (e.g., soil, peeling paint or Pb dust in older homes) throughout childhood. Such exposures may disproportionately affect susceptible populations, including pregnant women, children, and racial or ethnic minority groups that experience disparities in access to healthy housing or clean drinking water [10]
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