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Autism spectrum disorders (ASD) are pervasive neurodevelopmental disorders that affect an estimated 1 in 110 individuals. Although there is a strong genetic component associated with these disorders, this review focuses on the multifactorial nature of ASD and how different genome-wide (genomic) approaches contribute to our understanding of autism. Emphasis is placed on the need to study defined ASD phenotypes as well as to integrate large-scale “omics” data in order to develop a “systems-level” perspective of ASD, which in turn is necessary to allow predictions regarding responses to specific perturbations and interventions.