The mediation analysis of DNA methylation in the relationship between maternal arsenic exposure and neonatal birth weight
Objective To investigate whether the changes of DNA methylation level mediate the relationship between prenatal arsenic exposure and neonatal birth weight.Methods Data of this study were derived from the New Hampshire Birth Cohort Study,with 343 mother-infant pairs enrolled in the co-hort from February 2012 to September 2013 and available from the GEO database under accession number GSE71678.A total of 270 maternal and infant pairs were included in this study.The Sure independence screening(SIS)strategy and mediation analysis method were employed to estimate the mediation effect of DNA methylation sites between placental arsenic exposure and birth weight.Results After adjusting for maternal age,pre-pregnancy BMI,gestational diabetes mellitus,gestational age,infant gender,and placental tissue cell composition,25 DNA methylation sites were selected as candidate mediators.The re-sults of mediation analysis showed that after corrected by Bonferroni method.cg14900295 located on the VENTX gene was identified as a mediator between maternal arsenic exposure and low birth weight(ACME=0.057 6,95％CI:0.017 6-0.106 4,P=0.000 8).After corrected by FDR method,18 CpG loci were identified as mediators,among which cg03348978,cg02435495,cg09463047 and cg1 1862993 were all located on the HNF1B gene.Conclusions This study identified 18 specific sites where changes in DNA methylation levels play a crucial mediating role in the process linking prenatal arsenic exposure to low birth weight.Genes VENTX and HNF1B may be the key factors in the etiological mechanism.Therefore,these findings can provide a reference for revealing the genetic etiology mechanism of arsenic-induced low birth weight.
DNA methylationPlacental arsenic exposureBirth weightMediation effect
NETL
NSTL
万方数据
