TY - JOUR
T1 - Persistent DNA methylation changes associated with prenatal mercury exposure and cognitive performance during childhood
AU - Cardenas, Andres
AU - Rifas-Shiman, Sheryl L.
AU - Agha, Golareh
AU - Hivert, Marie France
AU - Litonjua, Augusto A.
AU - DeMeo, Dawn L.
AU - Lin, Xihong
AU - Amarasiriwardena, Chitra J.
AU - Oken, Emily
AU - Gillman, Matthew W.
AU - Baccarelli, Andrea A.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (R01 NR013945, R01 ES021357, R37 HD034568, K24 HD069408, R01 ES016314 and R01 HL 111108).
Publisher Copyright:
© The Author(s) 2017.
PY - 2017
Y1 - 2017
N2 - Prenatal exposure to mercury, a known neurotoxic metal, is associated with lower cognitive performance during childhood. Disruption of fetal epigenetic programming could explain mercury’s neurodevelopmental effects. We screened for epigenome-wide methylation differences associated with maternal prenatal blood mercury levels in 321 cord blood DNA samples and examined the persistence of these alterations during early (n = 75; 2.9–4.9 years) and mid-childhood (n = 291; 6.7–10.5 years). Among males, prenatal mercury levels were associated with lower regional cord blood DNA methylation at the Paraoxonase 1 gene (PON1) that persisted in early childhood and was attenuated in mid-childhood blood. Cord blood methylation at the PON1 locus predicted lower cognitive test scores measured during early childhood. Methylation at the PON1 locus was associated with PON1 expression in an independent set of cord blood samples. The observed persistent epigenetic disruption of the PON1 gene may modulate mercury toxicity in humans and might serve as a biomarker of exposure and disease susceptibility.
AB - Prenatal exposure to mercury, a known neurotoxic metal, is associated with lower cognitive performance during childhood. Disruption of fetal epigenetic programming could explain mercury’s neurodevelopmental effects. We screened for epigenome-wide methylation differences associated with maternal prenatal blood mercury levels in 321 cord blood DNA samples and examined the persistence of these alterations during early (n = 75; 2.9–4.9 years) and mid-childhood (n = 291; 6.7–10.5 years). Among males, prenatal mercury levels were associated with lower regional cord blood DNA methylation at the Paraoxonase 1 gene (PON1) that persisted in early childhood and was attenuated in mid-childhood blood. Cord blood methylation at the PON1 locus predicted lower cognitive test scores measured during early childhood. Methylation at the PON1 locus was associated with PON1 expression in an independent set of cord blood samples. The observed persistent epigenetic disruption of the PON1 gene may modulate mercury toxicity in humans and might serve as a biomarker of exposure and disease susceptibility.
UR - http://www.scopus.com/inward/record.url?scp=85030687225&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-00384-5
DO - 10.1038/s41598-017-00384-5
M3 - Article
C2 - 28325913
AN - SCOPUS:85030687225
SN - 2045-2322
VL - 7
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 288
ER -