Abstract Title: Exploring Molecular Mechanisms of Comorbidity: A Network-Based Analysis of ADHD and Autism
Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are two prevalent neurodevelopmental disorders (NDDs) that are frequently comorbid, posing significant challenges for diagnosis and treatment. Despite their distinct clinical profiles, they share several overlapping symptoms, suggesting common underlying genetic mechanisms. However, comprehensive research exploring this genetic overlap is still lacking.
In our ongoing study we have assembled lists of genes linked to both disorders with curated evidence trails for each. These lists currently contain approximately 1800 genes linked to ASD and 500 genes linked to ADHD. Since synaptic dysfunction is a key feature of both disorders, we are particularly interested in proteins expressed at the neuronal synapse where we have a comprehensive model based on over 50 published proteomic studies. The resulting network model integrates both the postsynaptic (4,817 proteins, 27,788 interactions) and presynaptic (2,221 proteins, 8,678 interactions) proteomes. Using the BioConductor packages BioNAR and SynaptomeDB, we have reconstructed a molecular network (protein-protein interaction) model of the synaptic proteome on which we have overlaid the genetic evidence lines for ASD and ADHD. We can then use these models to probe the molecular mechanisms common to both disorders (comorbidity) as well as identify molecular clusters more specifically associated with either disorder. Our findings aim to inform future research into disorder-specific and overlapping mechanisms and may have implications for biomarker discovery or therapeutic targeting.
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