Comparative gene expression analysis of lipid regulation pathways in brains of individuals with neurodevelopmental disorders

Autism Spectrum Disorder (ASD) is a behaviorally diagnosed neurodevelopmental disorder defined by deficits in social interaction and communication, as well as repetitive and restrictive behaviors. ASD is highly heritable, and recent studies show that it shares some genetic basis with other neurodevelopmental disorders, such as bipolar disease (BP), schizophrenia (SCZ), major depressive disorder (MDD), and obsessive-compulsive disorder (OCD). We have previously demonstrated an increased deleterious burden in lipid regulation genes in individuals with ASD as compared to their unaffected siblings. However, it is still unknown how these mutations might affect ASD brains. Here we compiled, harmonized, and integrated large datasets of gene expression data from postmortem brain tissue of individuals with ASD and genetically-overlapping neurodevelopmental disorders, as well as matched neurotypical individuals. We examined the expression of lipid regulation
pathways and mechanisms and found them to be significantly dysregulated across neurodevelopmental disorders, including ASD, SCZ, BP and MDD. Some mechanisms, such as lipoprotein metabolism, lipid metabolism and fatty acid biosynthesis, were consistently differentially expressed across cohorts, supporting their functional convergence among neurodevelopmental disorders.