Epigenetic modifications such as DNA methylation can begin to explain how environmental exposures in perinatal early life set up a gene expression signature that is remembered throughout life. The perinatal period is characterized by plasticity of both the nervous system and the immune system, wherein both systems are heavily dependent on appropriate environmental stimulation to reach maturity. What is not currently known is how specific environmental risk factors modify specific genetic loci involved in the maturation of the nervous and immune systems through epigenetic mechanisms. Though autism has a high rate of heritability in families, environmental factors such as shared in utero environment, birth order, maternal infections or medications also increase the relative risk for autism, demonstrating that environmental factors can modify genetic risk. The long-term goal of this project is to improve prevention, diagnosis, and treatment of autism through an integrative genetics approach of identifying specific epigenetic signatures of perinatal environmental risk and protective factors. The overall objective for this application is to identify genomic and methylomic correlates of human exposures and nutrition in a genome-wide focused prospective study of high-risk autism families in the MARBLES study.