Epigenetic mechanisms act at the interface of genetic and environmental risk factors in autism. Project 2 is designed to investigate to focus on the epigenetic mark of DNA niethylation, as environmental toxins have been demonstrated to reduce global DNA methylation levels while methyl-donor nutrients can be protective. This project will make use primarily of human cord blood samples from the MARBLES study in order to test the hypothesis that epigenetic patterns laid down in eariy life that regulate synapse maturation and immune responses will be impaired in autism through interactions between genetic and environmental factors.
The first aim i s designed to perform a genome-wide analysis of DNA methylation and copy number variation and to study the association of differences in genetics and epigenetics with environmental exposures (from Project 1 and Core C) and nutrients.
The second aim will investigate methylation of a specific gene locus, FOXP3, as an epigenetic marker of regulatory T cells and will make use of immunology expertise and existing participant samples from both MARBLES and CHARGE from Project 3.
The third aim will test a multifactorial mechanistic model of transcription-induced epigenetic memory of perinatal gene x environment interactions at two specific loci, F0XP3 and FMR1, through interactions with Projects 3 and 4. Together these studies will increase understanding of the epigenetic interface between genetic and environmental risk factors in autism, leading to improved diagnosis, prevention, and therapies.

Public Health Relevance

How early life exposures can shape the difference between a normal developmental trajectory and one that leads to autism spectrum disorders is the critical question addressed by this proposal. This project uses both genome-wide and gene focused mechanistic approaches on human samples from a prospective epidemiological study in order to improve understanding, prevention, and treatment of autism spectrum disorders.

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University of California Davis
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Fritsch, Erika B; Stegeman, John J; Goldstone, Jared V et al. (2015) Expression and function of ryanodine receptor related pathways in PCB tolerant Atlantic killifish (Fundulus heteroclitus) from New Bedford Harbor, MA, USA. Aquat Toxicol 159:156-66
Walker, Cheryl K; Krakowiak, Paula; Baker, Alice et al. (2015) Preeclampsia, placental insufficiency, and autism spectrum disorder or developmental delay. JAMA Pediatr 169:154-62
Harrington, Rebecca A; Lee, Li-Ching; Crum, Rosa M et al. (2014) Prenatal SSRI use and offspring with autism spectrum disorder or developmental delay. Pediatrics 133:e1241-8
Keil, Alexander P; Daniels, Julie L; Hertz-Picciotto, Irva (2014) Autism spectrum disorder, flea and tick medication, and adjustments for exposure misclassification: the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. Environ Health 13:3
Shelton, Janie F; Geraghty, Estella M; Tancredi, Daniel J et al. (2014) Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: the CHARGE study. Environ Health Perspect 122:1103-9
Piras, I S; Haapanen, L; Napolioni, V et al. (2014) Anti-brain antibodies are associated with more severe cognitive and behavioral profiles in Italian children with Autism Spectrum Disorder. Brain Behav Immun 38:91-9
Cao, Zhengyu; Cui, Yanjun; Nguyen, Hai M et al. (2014) Nanomolar bifenthrin alters synchronous Ca2+ oscillations and cortical neuron development independent of sodium channel activity. Mol Pharmacol 85:630-9
Medici, Valentina; Shibata, Noreene M; Kharbanda, Kusum K et al. (2014) Maternal choline modifies fetal liver copper, gene expression, DNA methylation, and neonatal growth in the tx-j mouse model of Wilson disease. Epigenetics 9:286-96
Akins, Roger S; Krakowiak, Paula; Angkustsiri, Kathleen et al. (2014) Utilization patterns of conventional and complementary/alternative treatments in children with autism spectrum disorders and developmental disabilities in a population-based study. J Dev Behav Pediatr 35:1-10
Pretto, Dalyir I; Kumar, Madhur; Cao, Zhengyu et al. (2014) Reduced excitatory amino acid transporter 1 and metabotropic glutamate receptor 5 expression in the cerebellum of fragile X mental retardation gene 1 premutation carriers with fragile X-associated tremor/ataxia syndrome. Neurobiol Aging 35:1189-97

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