Rights statement: This document is the Accepted Manuscript version of a Published Work that appeared in final form in Environmental Science and Technology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.est.0c01696
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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - DNA Methylation Biomarkers of IQ Reduction are Associated with Long-term Lead Exposure in School Aged Children in Southern China
AU - Wan, C.
AU - Pan, S.
AU - Lin, L.
AU - Li, J.
AU - Dong, G.
AU - Jones, K.C.
AU - Liu, F.
AU - Li, D.
AU - Liu, J.
AU - Yu, Z.
AU - Zhang, G.
AU - Ma, H.
N1 - This document is the Accepted Manuscript version of a Published Work that appeared in final form in Environmental Science and Technology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.est.0c01696
PY - 2021/1/5
Y1 - 2021/1/5
N2 - Although lead associated with intelligence decline in children has long been reported, studies combining intelligence determination, molecular mechanisms exploration, and biomarker screen are quite rare. In this study, based on 333 children aged 9-11, we determined the role of DNA methylation (DNAm) in the relationship of lead exposure with children's intelligence. DNAm was measured from children's blood DNA specimens, and mediation analysis was performed to identify DNAm biomarkers mediating the lead-intelligence relationship. We identified forty-three differentially methylated regions (DMRs), and two fragments (FAM50B1 and PTCHD3) significantly mediated the lead-intelligence relationship, with contribution rates of 30.36% (p = 0.010) and 60.36% (p <0.001), respectively. In addition, blood lead levels (BLLs) lower than 100 μg/L still adversely affected children's IQs and DNAm of the two fragments. Our data suggests that DNAm mediates lead-associated cognitive delay in children and blood lead reference value for school-aged children (100 μg/L) should be revised, and the candidate biomarkers can be used in related neurological diseases in future.
AB - Although lead associated with intelligence decline in children has long been reported, studies combining intelligence determination, molecular mechanisms exploration, and biomarker screen are quite rare. In this study, based on 333 children aged 9-11, we determined the role of DNA methylation (DNAm) in the relationship of lead exposure with children's intelligence. DNAm was measured from children's blood DNA specimens, and mediation analysis was performed to identify DNAm biomarkers mediating the lead-intelligence relationship. We identified forty-three differentially methylated regions (DMRs), and two fragments (FAM50B1 and PTCHD3) significantly mediated the lead-intelligence relationship, with contribution rates of 30.36% (p = 0.010) and 60.36% (p <0.001), respectively. In addition, blood lead levels (BLLs) lower than 100 μg/L still adversely affected children's IQs and DNAm of the two fragments. Our data suggests that DNAm mediates lead-associated cognitive delay in children and blood lead reference value for school-aged children (100 μg/L) should be revised, and the candidate biomarkers can be used in related neurological diseases in future.
KW - biomarkers
KW - blood lead
KW - children's intelligence
KW - DNA methylation
KW - FAM50B1
KW - PTCHD3
KW - Alkylation
KW - Blood
KW - DNA
KW - Methylation
KW - Blood lead level (BLLs)
KW - Contribution rate
KW - DNA Methylation
KW - Mediation analysis
KW - Molecular mechanism
KW - Neurological disease
KW - Reference values
KW - Southern China
KW - Biomarkers
U2 - 10.1021/acs.est.0c01696
DO - 10.1021/acs.est.0c01696
M3 - Journal article
VL - 55
SP - 412
EP - 422
JO - Environmental Science and Technology
JF - Environmental Science and Technology
SN - 0013-936X
IS - 1
ER -