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Epigenetic signatures at genomic sites sensitive to environmental exposures – potential applications for ASD research
Objectives: This talk will provide background on the field of epigenetic epidemiology and its relevance to ASDs. We will then focus on the potential for DNA methylation signatures, present in blood during childhood, that are associated with prenatal exposure to smoking, alcohol, maternal infection, folic acid, select serotonin reuptake inhibitors (SSRIs), and beta-2 adrenergic receptor (B2AR) medications.
Methods: Illumina Infinium450 BeadChip arrays were used to measure genome-scale methylation (> 485,000 loci) in blood of 609 children, aged 3-5, enrolled in the Study to Explore Early Development (SEED). Rigorous quality control measures were implemented. Prenatal exposure data were collected via telephone interview with the mother. For each exposure, regression analyses, adjusting for blood cell composition estimates, race, and age, were applied to identify novel sites of altered DNAm associated with exposure.
Results: Prenatal exposure data, including dose and timing where possible include active smoking (8%), alcohol (12%), folic acid (90%), B2AR(8%), and SSRI (8%) use as well as infection at any point during pregnancy (29%). Differentially methylated regions and composite signatures for each exposure will be presented. In addition, for prenatal smoking, examination of 26 loci previously shown to have differential methylation by maternal smoking in birth cord blood samples (Joubert et al. 2012), revealed striking concordance in our sample of 3-5 year olds; thus, we examined the persistence of these DNAm changes into childhood. These changes appear to be specific to tobacco exposure since the changes in DNAm at these 26 sites were not replicated when we examined prenatal exposure to infection, alcohol, B2AR or SSRI medications.
Conclusions: We show epigenetic signatures of prenatal environments, detectible in early childhood. These blood-derived DNAm measurements thus enable a more feasible sampling source and window for assessment of prenatal exposures for investigating exposure-disease relationships in ASD. This work is funded by the CDC, Autism Speaks, and NIEHS.
See more of: Epidemiology