Addiction Risk Polymorphisms Links Autism Spectrum Disorder with Reward Deficiency Syndrome: Insights from GWAS and Pharmacogenomic Meta Analyses

Autism Spectrum Disorder (ASD) is a complex syndrome with a plethora of clinical manifestations. Although such variability may be attributable to diverse genetic and epigenetic factors, mesolimbic dopaminergic reward pathways are consistently implicated in the illness’ course and neuropathobiology pointing to a need in an updated perspective on such a potential overlap area. To that end, we introduce a structured framework dissecting ASD's pathophysiology into stages while emphasizing the involvement of the classical reward structures. Through data mining of Genome-Wide Association Studies (GWAS) and in silico analyses, we uncovered genetic and epigenetic markers pointing to Reward Deficiency Syn-drome (RDS) component of ASD. We employ innovative approaches, including protein-protein interactions, gene regulatory networks, and systems biology analyses, to identify pathways and ASD gene ontologies. The multi-omics analysis integrates findings across genomics, proteomics, metabolomics, and phenomics, reinforcing the concept of ASD as an endophenotype of RDS. This comprehensive approach offers new insights into the genetic architecture and molecular mechanisms of ASD, paving the way for personalized medicine strategies thus yielding novel therapeutic interventions.