This grant provides support for an NIH Autism Center of Excellence (ACE). Early autism risk factors (genetics, familial, and environmental) lead to altered patterns of interaction between the child and his/her environment, which, in turn, can contribute to the abnormal development of neural circuitry and atypical behavior. This project has two major goals. First, it will identify autism susceptibility genes and their genomic location(s): genes in which variation affects risk for autism spectrum disorders (ASD). Second, it will seek to expand the set of component traits (endophenotypes) for which there is evidence for a genetic basis. The study will use an existing sample of families that have multiple members with an ASD diagnosis and also recruit additional relatives to identify genomic regions with ASD risk genes. Identification of susceptibility genes will lead to identification of underlying biological mechanisms and offers the promise of presymptomatic diagnosis and, ultimately, of disease-modifying medications or other therapies for use early in disease and during the presymptomatic period.