Characterisation of Cognitive Profiles in Autism Spectrum Disorder Using the Simons Simplex Collection

Background: The Simons Simplex Collection (SSC) is an ongoing study that aims to collect data on a total of 2000 families with one individual affected by an Autism Spectrum Disorder (ASD), otherwise known as simplex families. The SSC differs from other studies of ASD in that the focus is the collection of a sample enriched for denovo mutations, including deletions and duplications of genetic material. The relationship between cognitive profiles and ASD symptomatology has previously been described in ASD research in multiplex families; whereas similar investigation has never been explored in simplex families.
Objectives: This study aims to explore for phenotypic areas of interest for the genetic study of this simplex sample. Specifically, the relationship between the cognitive profiles and autism symptomatology of individuals with ASD in the SSC.  
Methods: The proposed analysis aims to examine cognitive profiles and their relationship to symptomatology in a large sample of children with ASD who participated in the SSC, a North American multiple site, university-based research study that includes approximately 420 families with only one child with an ASD.  The primary ineligibility criteria included severe to profound intellectual disability, severe cerebral palsy, extensive birth complications, Fragile X, or Down Syndrome in the proband, and a diagnosis of an ASD in the proband's first or second degree relatives or cousins.  Approximately 25% of the families in the SSC had one child with an ASD but no other children.   
Written consent and assent, as appropriate, was obtained separately for each family member prior to study enrollment. All family members enrolled in the study provided DNA samples and completed a standard assessment battery which included a series of parent interviews, a medical history interview, direct assessment of the proband, and completion of behavioral/cognitive questionnaires relevant to each family member.  All study probands were 4 -17 years of age and met criteria for a research diagnosis of an ASD, based on the Autism Diagnostic Interview-Revised (ADI-R), the Autism Diagnostic Observation Schedule (ADOS), and clinical consensus. 
Data from each site was merged into a common relational database designed by Prometheus Research, LLC, and DNA samples were stored at the Rutgers University Cell and DNA Repository.  

Results: This study will present the results of the analysis of the above data. Autism symptomatology measured using the ADI-R and ADOS will be related to the cognitive profiles of children expressing the ASD phenotype. Beyond the study of measured variables; exploratory factor and cluster analyses will be undertaken to look at the relationships of the cognitive “factors” (dimensions); and cognitive “cluster” (subtypes); with social communication impairment, language and repetitive behaviors.  The relationship of the severity of cognitive impairments, focusing on language impairment and milestones, will also be explored.

Conclusions: Findings from this study will provide evidence for any potential association between cognitive profile and phenotypic characteristics in ASD population. The results of this study along of the results found by other SSC phenotype committee will provide insight into understanding the pattern of autistic characteristics presented in affected children of similar genetic background.