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Quality control and statistical modeling for environmental epigenetics: A study on in utero lead exposure and DNA methylation at birth
Journal article   Open access   Peer reviewed

Quality control and statistical modeling for environmental epigenetics: A study on in utero lead exposure and DNA methylation at birth

Jaclyn M. Goodrich, Brisa N. Sanchez, Dana C. Dolinoy, Zhenzhen Zhang, Mauricio Hernandez-Avila, Howard Hu, Karen E. Peterson and Martha M. Tellez-Rojo
Epigenetics, v 10(1), pp 19-30
01 Jan 2015
DOI: https://doi.org/10.4161/15592294.2014.989077
PMID: 25580720
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://www.tandfonline.com/doi/pdf/10.4161/15592294.2014.989077?needAccess=trueView
Published, Version of Record (VoR) Open
url
https://doi.org/10.4161/15592294.2014.989077View
Published, Version of Record (VoR) Open

Abstract

Biochemistry & Molecular Biology Genetics & Heredity Life Sciences & Biomedicine Science & Technology
DNA methylation data assayed using pyrosequencing techniques are increasingly being used in human cohort studies to investigate associations between epigenetic modifications at candidate genes and exposures to environmental toxicants and to examine environmentally-induced epigenetic alterations as a mechanism underlying observed toxicant-health outcome associations. For instance, in utero lead (Pb) exposure is a neurodevelopmental toxicant of global concern that has also been linked to altered growth in human epidemiological cohorts; a potential mechanism of this association is through alteration of DNA methylation (e.g., at growth-related genes). However, because the associations between toxicants and DNA methylation might be weak, using appropriate quality control and statistical methods is important to increase reliability and power of such studies. Using a simulation study, we compared potential approaches to estimate toxicant-DNA methylation associations that varied by how methylation data were analyzed (repeated measures vs. averaging all CpG sites) and by method to adjust for batch effects (batch controls vs. random effects). We demonstrate that correcting for batch effects using plate controls yields unbiased associations, and that explicitly modeling the CpG site-specific variances and correlations among CpG sites increases statistical power. Using the recommended approaches, we examined the association between DNA methylation (in LINE-1 and growth related genes IGF2, H19 and HSD11B2) and 3 biomarkers of Pb exposure (Pb concentrations in umbilical cord blood, maternal tibia, and maternal patella), among mother-infant pairs of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort (n = 247). Those with 10 mu g/g higher patella Pb had, on average, 0.61% higher IGF2 methylation (P = 0.05). Sex-specific trends between Pb and DNA methylation (P < 0.1) were observed among girls including a 0.23% increase in HSD11B2 methylation with 10 mu g/g higher patella Pb.

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44 citations in Web of Science
46 citations in Scopus

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Genetics & Heredity
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