Persistent DNA methylation changes associated with prenatal mercury exposure and cognitive performance during childhood.
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.
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA. cardenas@hsph.harvard.edu.
Andres
A
Cardenas
Obesity Prevention Program, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Sheryl L
SL
Rifas-Shiman
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Golareh
G
Agha
Obesity Prevention Program, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Marie-France
MF
Hivert
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Augusto A
AA
Litonjua
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Dawn L
DL
DeMeo
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Xihong
X
Lin
Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Chitra J
CJ
Amarasiriwardena
Obesity Prevention Program, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Emily
E
Oken
Obesity Prevention Program, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Matthew W
0000-0001-9642-8797
MW
Gillman
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Andrea A
AA
Baccarelli
D043303:Aryldialkylphosphatase / Q000235:genetics; D003071:Cognition / Q000187:drug effects*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D008628:Mercury / Q000032:analysis / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D008628:Mercury