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The Capital Region of Denmark - a part of Copenhagen University Hospital
E-pub ahead of print

Transcriptomic networks implicate neuronal energetic abnormalities in three mouse models harboring autism and schizophrenia-associated mutations

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  1. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

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  2. Autism spectrum disorder and attention deficit hyperactivity disorder have a similar burden of rare protein-truncating variants

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  3. Clinical association to FKBP5 rs1360780 in patients with depression

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  4. A large-scale genomic investigation of susceptibility to infection and its association with mental disorders in the Danish population

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  5. Genetic risk scores for major psychiatric disorders and the risk of postpartum psychiatric disorders

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Genetic risk for psychiatric illness is complex, so identification of shared molecular pathways where distinct forms of genetic risk might coincide is of substantial interest. A growing body of genetic and genomic studies suggest that such shared molecular pathways exist across disorders with different clinical presentations, such as schizophrenia and autism spectrum disorder (ASD). But how this relates to specific genetic risk factors is unknown. Further, whether some of the molecular changes identified in brain relate to potentially confounding antemortem or postmortem factors are difficult to prove. We analyzed the transcriptome from the cortex and hippocampus of three mouse lines modeling human copy number variants (CNVs) associated with schizophrenia and ASD: Df(h15q13)/+, Df(h22q11)/+, and Df(h1q21)/+ which carry the 15q13.3 deletion, 22q11.2 deletion, and 1q21.1 deletion, respectively. Although we found very little overlap of differential expression at the level of individual genes, gene network analysis identified two cortical and two hippocampal modules of co-expressed genes that were dysregulated across all three mouse models. One cortical module was associated with neuronal energetics and firing rate, and overlapped with changes identified in postmortem human brain from SCZ and ASD patients. These data highlight aspects of convergent gene expression in mouse models harboring major risk alleles, and strengthen the connection between changes in neuronal energetics and neuropsychiatric disorders in humans.

Original languageEnglish
JournalMolecular Psychiatry
ISSN1359-4184
DOIs
Publication statusE-pub ahead of print - 8 Nov 2019

ID: 58572905