Prenatal mercury concentration is associated with changes in DNA methylation at TCEANC2 in newborns

Kelly M. Bakulski, Hwa Jin Lee, Jason I. Feinberg, Ellen M. Wells, Shannon Brown, Julie B. Herbstman, Frank R. Witter, Rolf Halden, Kathleen Caldwell, Mary Ellen Mortensen, Andrew E. Jaffe, John Moye, Laura E. Caulfield, Yi Pan, Lynn R. Goldman, Andrew P. Feinberg, M. Daniele Fallin

Research output: Contribution to journalArticle

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Abstract

Background: Human exposure to the widespread environmental contaminant mercury is a known risk factor for common diseases such as cancer, cardiovascular disease and neurological disorders through poorly characterized mechanisms. Evidence suggests mercury exposure may alter DNA methylation levels, but to date, the effects in early life on a genome-wide scale have not been investigated. Methods: A study sample of 141 newborns was recruited in Baltimore, MD, USA and total mercury and methylmercury were measured in cord blood samples. We quantified genome-wide DNA methylation data using CHARM 2.0, an array-based method, and used region-finding analyses to identify concentration-associated differentially methylated regions (DMRs). To test for replication of these identified DMRs in the pilot, or Vanguard, phase of the National Children's Study (NCS), we compared bisulfitepyrosequenced DNA at candidate regions from 85 whole cord blood samples with matched first trimester maternal mercury concentration measures. Results: Total mercury concentration was associated with methylation at DMRs inside ANGPT2 and near PRPF18 genes [false discovery rate (FDR) <0.05], as well as DMRs near FOXD2 and within TCEANC2 (FDR<0.1) genes. Methylmercury concentration was associated with an overlapping DMR within TCEANC2 (FDR<0.05). In NCS replication analyses, methylation levels at three of four cytosine-guanine DNA dinucleotides (CpG sites) within the TCEANC2 DMR were associated with total mercury concentration (P

Original languageEnglish (US)
Pages (from-to)1249-1262
Number of pages14
JournalInternational Journal of Epidemiology
Volume44
Issue number4
DOIs
StatePublished - Aug 1 2015

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DNA Methylation
Mercury
Newborn Infant
Fetal Blood
Methylation
Genome
Baltimore
DNA
Genetic Association Studies
First Pregnancy Trimester
Nervous System Diseases
Cardiovascular Diseases
Mothers
Genes
Neoplasms

Keywords

  • Cord blood
  • DNA methylation
  • Epigenetics
  • Mercury exposure
  • Methylmercury

ASJC Scopus subject areas

  • Epidemiology

Cite this

Bakulski, K. M., Lee, H. J., Feinberg, J. I., Wells, E. M., Brown, S., Herbstman, J. B., ... Daniele Fallin, M. (2015). Prenatal mercury concentration is associated with changes in DNA methylation at TCEANC2 in newborns. International Journal of Epidemiology, 44(4), 1249-1262. https://doi.org/10.1093/ije/dyv032

Prenatal mercury concentration is associated with changes in DNA methylation at TCEANC2 in newborns. / Bakulski, Kelly M.; Lee, Hwa Jin; Feinberg, Jason I.; Wells, Ellen M.; Brown, Shannon; Herbstman, Julie B.; Witter, Frank R.; Halden, Rolf; Caldwell, Kathleen; Mortensen, Mary Ellen; Jaffe, Andrew E.; Moye, John; Caulfield, Laura E.; Pan, Yi; Goldman, Lynn R.; Feinberg, Andrew P.; Daniele Fallin, M.

In: International Journal of Epidemiology, Vol. 44, No. 4, 01.08.2015, p. 1249-1262.

Research output: Contribution to journalArticle

Bakulski, KM, Lee, HJ, Feinberg, JI, Wells, EM, Brown, S, Herbstman, JB, Witter, FR, Halden, R, Caldwell, K, Mortensen, ME, Jaffe, AE, Moye, J, Caulfield, LE, Pan, Y, Goldman, LR, Feinberg, AP & Daniele Fallin, M 2015, 'Prenatal mercury concentration is associated with changes in DNA methylation at TCEANC2 in newborns', International Journal of Epidemiology, vol. 44, no. 4, pp. 1249-1262. https://doi.org/10.1093/ije/dyv032
Bakulski, Kelly M. ; Lee, Hwa Jin ; Feinberg, Jason I. ; Wells, Ellen M. ; Brown, Shannon ; Herbstman, Julie B. ; Witter, Frank R. ; Halden, Rolf ; Caldwell, Kathleen ; Mortensen, Mary Ellen ; Jaffe, Andrew E. ; Moye, John ; Caulfield, Laura E. ; Pan, Yi ; Goldman, Lynn R. ; Feinberg, Andrew P. ; Daniele Fallin, M. / Prenatal mercury concentration is associated with changes in DNA methylation at TCEANC2 in newborns. In: International Journal of Epidemiology. 2015 ; Vol. 44, No. 4. pp. 1249-1262.
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AU - Mortensen, Mary Ellen

AU - Jaffe, Andrew E.

AU - Moye, John

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AU - Pan, Yi

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AU - Daniele Fallin, M.

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