Dynamic expression of genes associated with schizophrenia and bipolar disorder across development

Clifton, Nicholas E. ORCID: https://orcid.org/0000-0003-2597-5253, Hannon, Eilis ORCID: https://orcid.org/0000-0001-6840-072X, Harwood, Janet C., Di Florio, Arianna ORCID: https://orcid.org/0000-0003-0338-2748, Thomas, Kerrie L. ORCID: https://orcid.org/0000-0003-3355-9583, Holmans, Peter A. ORCID: https://orcid.org/0000-0003-0870-9412, Walters, James T. R. ORCID: https://orcid.org/0000-0002-6980-4053, O'Donovan, Michael ORCID: https://orcid.org/0000-0001-7073-2379, Owen, Michael J. ORCID: https://orcid.org/0000-0003-4798-0862, Pocklington, Andrew J. ORCID: https://orcid.org/0000-0002-2137-0452 and Hall, Jeremy ORCID: https://orcid.org/0000-0003-2737-9009 2019. Dynamic expression of genes associated with schizophrenia and bipolar disorder across development. Translational Psychiatry 9 , 74. 10.1038/s41398-019-0405-x

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Abstract

Common genetic variation contributes a substantial proportion of risk for both schizophrenia and bipolar disorder. Furthermore, there is evidence of significant, but not complete, overlap in genetic risk between the two disorders. It has been hypothesised that genetic variants conferring risk for these disorders do so by influencing brain development, leading to the later emergence of symptoms. The comparative profile of risk gene expression for schizophrenia and bipolar disorder across development over different brain regions however remains unclear. Using genotypes derived from genome-wide associations studies of the largest available cohorts of patients and control subjects, we investigated whether genes enriched for schizophrenia and bipolar disorder association show a bias for expression across any of 13 developmental stages in prefrontal cortical and subcortical brain regions. We show that genetic association with schizophrenia is positively correlated with expression in the prefrontal cortex during early midfetal development and early infancy, and negatively correlated with expression during late childhood, which stabilises in adolescence. In contrast, risk-associated genes for bipolar disorder did not exhibit a bias towards expression at any prenatal stage, although the pattern of postnatal expression was similar to that of schizophrenia. These results highlight the dynamic expression of genes harbouring risk for schizophrenia and bipolar disorder across prefrontal cortex development and support the hypothesis that prenatal neurodevelopmental events are more strongly associated with schizophrenia than bipolar disorder.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Advanced Research Computing @ Cardiff (ARCCA) Medicine Biosciences MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information:	This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher:	Springer Nature
ISSN:	2158-3188
Date of First Compliant Deposit:	14 November 2018
Date of Acceptance:	13 November 2018
Last Modified:	18 Jun 2024 01:05
URI:	https://orca.cardiff.ac.uk/id/eprint/116786

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