Abstract
The identification of genomic signatures that aid early identification of individuals at risk for autism spectrum disorder (ASD) in the toddler period remains a major challenge because of the genetic and phenotypic heterogeneity of the disorder. Generally, ASD is not diagnosed before the fourth to fifth birthday.

To apply a functional genomic approach to identify a biologically relevant signature with promising performance in the diagnostic classification of infants and toddlers with ASD.
Proof-of-principle study of leukocyte RNA expression levels from 2 independent cohorts of children aged 1 to 4 years (142 discovery participants and 73 replication participants) using Illumina microarrays. Coexpression analysis of differentially expressed genes between Discovery ASD and control toddlers were used to define gene modules and eigengenes used in a diagnostic classification analysis. Independent validation of the classifier performance was tested on the replication cohort. Pathway enrichment and protein-protein interaction analyses were used to confirm biological relevance of the functional networks in the classifier. Participant recruitment occurred in general pediatric clinics and community settings. Male infants and toddlers (age range, 1-4 years) were enrolled in the study. Recruitment criteria followed the 1-Year Well-Baby Check-Up Approach. Diagnostic judgment followed DSM-IV-TR and Autism Diagnostic Observation Schedule criteria for autism. Participants with ASD were compared with control groups composed of typically developing toddlers as well as toddlers with global developmental or language delay.