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Transcriptome Analysis of Cortical Tissue Reveals Shared Sets of Down-Regulated Genes in Autism and Schizophrenia

View ORCID ProfileShannon E. Ellis, Rebecca Panitch, Andrew B. West, Dan E. Arking
doi: https://doi.org/10.1101/029132
Shannon E. Ellis
1McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
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Rebecca Panitch
1McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
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Andrew B. West
2Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
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Dan E. Arking
1McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
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ABSTRACT

Autism (AUT), Schizophrenia (SCZ), and bipolar disorder (BPD) are three highly heritable neuropsychiatric conditions. Clinical similarities and genetic overlap between the three disorders have been reported; however, the causes and the downstream effects of this overlap remain elusive. By analyzing transcriptomic RNA-Sequencing data generated from post-mortem cortical brain tissues from AUT, SCZ, BPD and control subjects, we have begun to characterize the extent of gene expression overlap between these disorders. We report that the AUT and SCZ transcriptomes are significantly correlated (p<0.001), while the other two cross disorder comparisons (AUT-BPD, SCZ-BPD) are not. Among AUT and SCZ, we find that the genes differentially expressed across disorders are involved in neurotransmission and synapse regulation. Despite lack of global transcriptomic overlap across all three disorders, we highlight two genes, IQSEC3 and COPS7A, which are significantly down-regulated compared to controls across all three disorders, suggesting either shared etiology or compensatory changes across these neuropsychiatric conditions. Finally, we tested for enrichment of genes differentially expressed across disorders in genetic association signals in AUT, SCZ or BPD, reporting lack of signal in any of the previously published GWAS. Together, these studies highlight the importance of examining gene expression from the primary tissue involved in neuropsychiatric conditions, cortical brain. We identify a shared role for altered neurotransmission and synapse regulation in AUT and SCZ, in addition to two genes that may more generally contribute to neurodevelopmental and neuropsychiatric conditions.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 18, 2016.
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Transcriptome Analysis of Cortical Tissue Reveals Shared Sets of Down-Regulated Genes in Autism and Schizophrenia
Shannon E. Ellis, Rebecca Panitch, Andrew B. West, Dan E. Arking
bioRxiv 029132; doi: https://doi.org/10.1101/029132
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Transcriptome Analysis of Cortical Tissue Reveals Shared Sets of Down-Regulated Genes in Autism and Schizophrenia
Shannon E. Ellis, Rebecca Panitch, Andrew B. West, Dan E. Arking
bioRxiv 029132; doi: https://doi.org/10.1101/029132

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