PROJECT SUMMARY/ABSTRACT This project builds on recent research in our laboratory that showed for the first time that genes directly shape the way a child sees the world: what a child spends time looking at?as well as how, when, and where she looks?are all strongly influenced by genetic variation (Constantino et al, Nature, 2017). Identical twins, who share the same genetic variation, effectively synchronize their looking to social content. Moreover, these same measures of social looking are markedly and differentially decreased in children with autism spectrum disorder (ASD) (?2= 64.03, P < 0.0001). In the current project, we will measure genetic and environmental influence on social visual engagement and brain growth from birth through toddlerhood, quantifying effects of gene- environment transactions over time. We will use eye-tracking to measure how infants look at the social world and MRI to measure changing brain connectivity under conditions of controlled genetic variation: identical & fraternal twins followed from the first week after birth. We will enroll 240 twins (120 pairs), collecting eye- tracking data at 10 time points, neuroimaging data at 5 time points, and standardized assessments of social- communicative competency at 3 time points. This application will test the hypothesis that gene-by- environment-by-age transactions in the first years of life serve as a powerful developmental canalizing mechanism, a mechanism capable of providing the necessary shared medium for typical social development, and yet equally capable of channeling diverse initial liabilities off-course, into atypical social development resulting in the syndromic social disability called autism spectrum disorder. By quantifying the developmental timing of gene-environment transactions, together with their impact on phenotypic presentation of social behavior and brain growth, this project will provide insights into modifiable behavioral pathways that offer the greatest therapeutic potential to prevent or preempt the emergence of deleterious consequences of atypical development as found in ASD and other neurodevelopmental disabilities.