Independent Maternal and Fetal Genetic Effects on Midgestational Circulating Levels of Environmental Pollutants.
Traglia M, Croen LA, Lyall K et al.
Publication Details
Comprehensive information about this research publication
Abstract
Summary of the research findings
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 midpregnancy 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 midpregnancy 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 = 7.8 × 10-11) in the CYP2B6 gene and for BDE-28 (P = 3.2 × 10-8) near the SH3GL2 gene, both involved in xenobiotic and lipid metabolism. Fetal genetic loci contributed to the levels of BDE-100 (P = 4.6 × 10-8) and PCB187 (P = 2.8 × 10-8), 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 midgestational biomarkers for environmental exposures by nonoverlapping 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.
329 Hispanic mothers, 273 European ancestry mothers, 122 Asian ancestry mothers, 23 South Asian ancestry mothers, 21 African American mothers, 22 other ancestry mothers
Study Statistics
Key metrics and study information
Analysis
Comprehensive review of health and genetic findings
Important Disclaimer: This review has been performed semi-automatically and is provided for informational purposes only. While we strive for accuracy, this analysis may contain errors, omissions, or misinterpretations of the original research. DNA Genics disclaims all liability for any inaccuracies, errors, or consequences arising from the use of this information. Users should independently verify all information and consult original research publications before making any decisions based on this content. This analysis is not intended as a substitute for professional scientific review or medical advice.
Analysis In Progress
Our analysis of this publication is currently being prepared. Please check back soon for comprehensive insights into the health and genetic findings discussed in this research.