Developmental Profile of Psychiatric Risk Associated With Voltage-Gated Cation Channel Activity
| Autor: | Jeremy Hall, Michael Conlon O'Donovan, Daniel R. Weinberger, Michael John Owen, Nicholas E. Clifton, James T.R. Walters, Janet C Harwood, Leonardo Collado-Torres, Antonio F. Pardiñas, Arianna Di Florio, Peter Holmans, Emily E. Burke, Andrew E. Jaffe |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adult medicine.medical_specialty Bipolar Disorder Genome-wide association study Biology Genome-wide association studies Voltage-gated cation channel activity 03 medical and health sciences 0302 clinical medicine Cations medicine Humans Genetic Predisposition to Disease Bipolar disorder Psychiatry Biological Psychiatry Psychiatric genetics Genetic association Depressive Disorder Major Mental Disorders medicine.disease Brain development Potassium channel activity Archival Report 030104 developmental biology Schizophrenia Major depressive disorder Dorsolateral prefrontal cortex Psychiatric disorders Transcriptome 030217 neurology & neurosurgery Cation channel activity Genome-Wide Association Study |
| Zdroj: | Biological Psychiatry |
| ISSN: | 1873-2402 0006-3223 |
| Popis: | BackgroundRecent breakthroughs in psychiatric genetics have implicated biological pathways onto which genetic risk for psychiatric disorders converges. However, these studies do not reveal the developmental time point(s) at which these pathways are relevant.MethodsWe aimed to determine the relationship between psychiatric risk and developmental gene expression relating to discrete biological pathways. We used post-mortem RNA sequencing data (BrainSeq and BrainSpan) from brain tissue at multiple pre- and post-natal timepoints and summary statistics from recent genome-wide association studies of schizophrenia, bipolar disorder and major depressive disorder. We prioritised gene sets for overall enrichment of association with each disorder, and then tested the relationship between the association of each of their constituent genes with their relative expression at each developmental stage.ResultsWe observed relationships between the expression of genes involved involtage-gated cation channel activityduring Early Midfetal, Adolescence and Early Adulthood timepoints and association with schizophrenia and bipolar disorder, such that genes more strongly associated with these disorders had relatively low expression during Early Midfetal development and higher expression during Adolescence and Early Adulthood. The relationship with schizophrenia was strongest for the subset of genes related to calcium channel activity, whilst for bipolar disorder the relationship was distributed between calcium and potassium channel activity genes.ConclusionsOur results indicate periods during development when biological pathways related to the activity of calcium and potassium channels may be most vulnerable to the effects of genetic variants conferring risk to psychiatric disorders. Furthermore, they indicate key time points and potential targets for disorder-specific therapeutic interventions. |
| Databáze: | OpenAIRE |
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