The central hypothesis for the proposed research is that a collaborative translational autism research program with the military will result in the improved diagnosis and care of those enrolled in the study and enhance biomedical research on the diagnosis, causes, and treatment of autism spectrum disorders (ASD), in general. With approved revised Specific Aims, during this project, we enrolled 65 families (259 individuals) in the existing Central Ohio Registry for Autism, including 26 families from Wright-Patterson Air Force Base. Ninety-six percent of these families had a chromosomal microarray analysis performed. Exome sequencing was performed on 210 individuals from Autism I and II with the identification of 7 clinically relevant likely pathogenic variants in probands related to their ASD diagnosis. Transcriptome analysis and subsequent analysis in Central Ohio Registry for Autism trios of 14 single nucleotide polymorphisms in relevant genes found a significant association between a variant in the serotonin receptor 2A gene that modulates its expression. Preliminary data also suggest an association between ASD and the immune-related genes C4A and DEFA3. Finally, using a mouse model for an X-linked gene involved in cholesterol synthesis, we demonstrated behavioral abnormalities consistent with a role for the pathway in neural development and, perhaps, ASD.