Medicina Molecular e Genética

Genetic Insights from a Molecular Pathway Analysis on Two Independent Samples of Autistic Patients

Abstract

Drago A, Calabro M, Crisafulli C and Rasmussen SK

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by limited interest and lacking ability in social interactions, repetitive behavior and dysfunction in social communication. ASD runs in families. Twin studies suggest a strong genetic basis for ASD. The complete definition of a genetic profile at risk for ASD is nevertheless currently lacking.
Methods: NIHM-Autism datasets 3 and 4 (n=1233 and n=2890 respectively) were analyzed. A molecular pathway analysis was conducted. Quality analysis was run as usual (λ values). Plink and R (ReactomePA and Bioconductor packages) served for TDT, association tests and the molecular pathway analysis.
Results and Discussion: The “Adherens junctions’ interactions pathway” and “Axon guidance” were enriched in the first sample, while the “Extracellular matrix organization pathway” was enriched in the second sample. The “Axon guidance pathway” showed a trend for enrichment in the second sample. A trend of significant enrichment was observed for the “NCAM1 molecular pathway” when the severity of autistic symptoms was investigated.
Conclusion: Cell to cell interaction and the cell-matrix interaction may hold the genetic risk for ASD. Both neurodevelopment and immune response (T-cell) rely on those processes and may be involved in the pathophysiology of ASD.