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

Published

Journal Article

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), whereas the other two cross-disorder comparisons (AUT-BPD and 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 the lack of global transcriptomic overlap across all three disorders, we highlight two genes, IQSEC3 and COPS7A, which are significantly downregulated compared with 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 genome-wide association study (GWAS). Together, these studies highlight the importance of examining gene expression from the primary tissue involved in neuropsychiatric conditions-the 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.

Full Text

Duke Authors

Cited Authors

  • Ellis, SE; Panitch, R; West, AB; Arking, DE

Published Date

  • May 24, 2016

Published In

Volume / Issue

  • 6 /

Start / End Page

  • e817 -

PubMed ID

  • 27219343

Pubmed Central ID

  • 27219343

Electronic International Standard Serial Number (EISSN)

  • 2158-3188

International Standard Serial Number (ISSN)

  • 2158-3188

Digital Object Identifier (DOI)

  • 10.1038/tp.2016.87

Language

  • eng