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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. A major role for common genetic variation in anxiety disorders

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  2. Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

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  3. Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank

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  4. Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression

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  1. Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder

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  2. Co-occurring hydrocephalus in autism spectrum disorder: a Danish population-based cohort study

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  3. A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis

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  4. Copy Number Variants and Polygenic Risk Scores Predict Need of Care in Autism and/or ADHD Families

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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