Shared sets of genes downregulated in autism and schizophrenia

Transcriptomic relationships between disorders:  Correlation of differentially expressed genes for (a) autism (AUT) and schizophrenia (SCZ) and (b) AUT and bipolar disorder (BPD). The best fit line is in red; R = Pearson’s Correlation Coefficient. Image from Ellis S.E. et al. (2016).
A number of genetic studies based on analysis of DNA derived from blood or saliva have demonstrated an overlap between single-nucleotide polymorphisms associated with schizophrenia and bipolar disorder, and, to a lesser extent, between those associated with schizophrenia and autism.  Fewer studies at the level of gene expression have been performed, however, due to the limited availability of tissue from the affected organ — the brain — of individuals with these disorders. SFARI Investigator Dan Arking previously performed a large-scale RNA-sequencing study that compared the transcriptomes of postmortem cortical tissue samples from people with autism and neurotypical individuals (Gupta et al., 2014). The current study expanded on this effort by comparing these data to RNA-sequencing data from individuals with schizophrenia or bipolar disorder.  A significant correlation was observed between autism and schizophrenia transcriptomes (but not between the other cross-disorder comparisons).  Pathway analyses revealed that the genes differentially expressed in autism and schizophrenia are involved in neurotransmission and synaptic development, suggesting a shared etiology. With the help of initiatives such as Autism BrainNet, the NIH NeuroBioBank and other tissue repositories, larger sample sizes will become available, enabling more detailed studies of gene expression changes in neurodevelopmental and neuropsychiatric disorders.


Transcriptome analysis of cortical tissue reveals shared sets of downregulated genes in autism and schizophrenia.

Ellis S.E., Panitch R., West A.B., Arking D.

Transl. Psychiatry 6, e817 (May 23, 2016) PubMed

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