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Neonatal Lead (Pb) Exposure and DNA Methylation Profiles in Dried Bloodspots

Luke Montrose, Jaclyn M. Goodrich, Masako Morishita, Joseph Kochmanski, Zachary Klaver, Raymond Cavalcante, Julie C. Lumeng, Karen E. Peterson and Dana C. Dolinoy
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Luke Montrose: Department of Community and Environmental Health, Boise State University, Boise, ID 83725, USA
Jaclyn M. Goodrich: Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109, USA
Masako Morishita: Department of Family Medicine, Michigan State University, East Lansing, MI 48824, USA
Joseph Kochmanski: Department of Translational Neuroscience, Michigan State University, Grand Rapids, MI 49503, USA
Zachary Klaver: Department of Family Medicine, Michigan State University, East Lansing, MI 48824, USA
Raymond Cavalcante: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
Julie C. Lumeng: Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA
Karen E. Peterson: Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109, USA
Dana C. Dolinoy: Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109, USA

IJERPH, 2020, vol. 17, issue 18, 1-17

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.

Keywords: exposure assessment; epigenomics; neonatal bloodspots; metals; developmental origins of health and disease; biomarkers (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2020
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