domingo, 5 de marzo de 2017

Independent Maternal and Fetal Genetic Effects on Mid-gestational Circulating Levels of Environmental Pollutants. - PubMed - NCBI

Independent Maternal and Fetal Genetic Effects on Mid-gestational Circulating Levels of Environmental Pollutants. - PubMed - NCBI



 2017 Feb 24. pii: g3.117.039784. doi: 10.1534/g3.117.039784. [Epub ahead of print]

Independent Maternal and Fetal Genetic Effects on Mid-gestational Circulating Levels of Environmental Pollutants.

Abstract

Maternal exposure to environmental pollutants could affect fetal brain development and increase autism spectrum disorder (ASD) risk in conjunction with differential genetic susceptibility. Organohalogen congeners measured in maternal mid-pregnancy blood samples have recently shown significant, but negative associations with offspring ASD outcome. We report the first large scale maternal and fetal genetic study of the mid-pregnancy serum levels of a set of 21 organohalogens in a subset of 790 genotyped women and 764 children collected in California by the Early Markers for Autism (EMA) Project. Levels of PCB (polychlorinated biphenyl) and PBDE (polybrominated diphenyl ether) congeners showed high maternal and fetal estimated SNP-based heritability (h2g ) accounting for 39-99% of the total variance. Genome-wide association analyses identified significant maternal loci for p,p'-DDE (P=7.8x10-11) in the CYP2B6 gene and for BDE-28 (P=3.2x10-8) near the SH3GL2 gene, both involved in xenobiotic and lipid metabolism. Fetal genetic loci contributed to the levels of BDE-100 (P=4.6x10-8) and PCB187 (P=2.8x10-8), near the potential metabolic genes LOXHD1 and PTPRD, previously implicated in neurodevelopment. Negative associations were observed for BDE-100, BDE153, and the sum of PBDEs with ASD, partly explained by genome-wide additive genetic effects that predicted PBDE levels. Our results support genetic control of mid-gestational biomarkers for environmental exposures by non-overlapping maternal and fetal genetic determinants, suggesting that future studies of environmental risk factors should take genetic variation into consideration. The independent influence of fetal genetics supports previous hypotheses that fetal genotypes expressed in placenta can influence maternal physiology and the transplacental transfer of organohalogens.

KEYWORDS:

GWAS; autism spectrum disorders; environmental pollutants; heritability; metabolism

PMID:
 
28235828
 
DOI:
 
10.1534/g3.117.039784

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From HuGE Literature Finder Database
This database contains published literature on genetic associations and other human genome epidemiology

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