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DNA methylation changes associated with prenatal mercury exposure : A meta-analysis of prospective cohort studies from PACE consortium

Lozano, Manuel ; Yousefi, Paul ; Broberg, Karin LU orcid ; Soler-Blasco, Raquel ; Miyashita, Chihiro ; Pesce, Giancarlo ; Kim, Woo Jin ; Rahman, Mohammad ; Bakulski, Kelly M. and Haug, Line S. , et al. (2022) In Environmental Research 204.
Abstract

Mercury (Hg) is a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n = 1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n = 794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (β = 2.28 × 10−4, p-value = 5.87 × 10−5) in relation to prenatal MeHg... (More)

Mercury (Hg) is a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n = 1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n = 794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (β = 2.28 × 10−4, p-value = 5.87 × 10−5) in relation to prenatal MeHg exposure. In child blood, we identified differential DNAm at cg15288800 (β = 0.004, p-value = 4.97 × 10−5), also located in MED31. This repeated link to MED31, a gene involved in lipid metabolism and RNA Polymerase II transcription function, may suggest a DNAm perturbation related to MeHg exposure that persists into early childhood. Further, we found evidence for association between prenatal MeHg exposure and child blood DNAm levels at two additional CpGs: cg12204245 (β = 0.002, p-value = 4.81 × 10−7) in GRK1 and cg02212000 (β = −0.001, p-value = 8.13 × 10−7) in GGH. Prenatal MeHg exposure was associated with DNAm modifications that may influence health outcomes, such as cognitive or anthropometric development, in different populations.

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@article{728be5ae-c0a1-42d4-920b-0c17c838381c,
  abstract     = {{<p>Mercury (Hg) is a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n = 1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n = 794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (β = 2.28 × 10<sup>−4</sup>, p-value = 5.87 × 10<sup>−5</sup>) in relation to prenatal MeHg exposure. In child blood, we identified differential DNAm at cg15288800 (β = 0.004, p-value = 4.97 × 10<sup>−5</sup>), also located in MED31. This repeated link to MED31, a gene involved in lipid metabolism and RNA Polymerase II transcription function, may suggest a DNAm perturbation related to MeHg exposure that persists into early childhood. Further, we found evidence for association between prenatal MeHg exposure and child blood DNAm levels at two additional CpGs: cg12204245 (β = 0.002, p-value = 4.81 × 10<sup>−7</sup>) in GRK1 and cg02212000 (β = −0.001, p-value = 8.13 × 10<sup>−7</sup>) in GGH. Prenatal MeHg exposure was associated with DNAm modifications that may influence health outcomes, such as cognitive or anthropometric development, in different populations.</p>}},
  author       = {{Lozano, Manuel and Yousefi, Paul and Broberg, Karin and Soler-Blasco, Raquel and Miyashita, Chihiro and Pesce, Giancarlo and Kim, Woo Jin and Rahman, Mohammad and Bakulski, Kelly M. and Haug, Line S. and Ikeda-Araki, Atsuko and Huel, Guy and Park, Jaehyun and Relton, Caroline and Vrijheid, Martine and Rifas-Shiman, Sheryl and Oken, Emily and Dou, John F. and Kishi, Reiko and Gutzkow, Kristine B. and Annesi-Maesano, Isabella and Won, Sungho and Hivert, Marie France and Fallin, M. Daniele and Vafeiadi, Marina and Ballester, Ferran and Bustamante, Mariona and Llop, Sabrina}},
  issn         = {{0013-9351}},
  keywords     = {{ALSPAC; DNA methylation; HELIX study; Mercury; Methylmercury; PACE; Prenatal exposure}},
  language     = {{eng}},
  month        = {{03}},
  publisher    = {{Elsevier}},
  series       = {{Environmental Research}},
  title        = {{DNA methylation changes associated with prenatal mercury exposure : A meta-analysis of prospective cohort studies from PACE consortium}},
  url          = {{http://dx.doi.org/10.1016/j.envres.2021.112093}},
  doi          = {{10.1016/j.envres.2021.112093}},
  volume       = {{204}},
  year         = {{2022}},
}