Abstract
BACKGROUND: Mounting evidence shows genetic overlap between multiple psychiatric disorders. However, the biological underpinnings of shared risk for psychiatric disorders are not yet fully uncovered. The identification of underlying biological mechanisms is crucial for the progress in the treatment of these disorders.
METHODS: We applied gene-set analysis including 7372 gene sets, and 53 tissue-type specific gene-expression profiles to identify sets of genes that are involved in the etiology of multiple psychiatric disorders. We included genome-wide meta-association data of the five psychiatric disorders schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, and attention-deficit/hyperactivity disorder. The total dataset contained 159 219 cases and 262 481 controls.
RESULTS: We identified 19 gene sets that were significantly associated with the five psychiatric disorders combined, of which we excluded five sets because their associations were likely driven by schizophrenia only. Conditional analyses showed independent effects of several gene sets that in particular relate to the synapse. In addition, we found independent effects of gene expression levels in the cerebellum and frontal cortex.
CONCLUSIONS: We obtained novel evidence for shared biological mechanisms that act across psychiatric disorders and we showed that several gene sets that have been related to individual disorders play a role in a broader range of psychiatric disorders.
| Original language | English |
|---|---|
| Pages (from-to) | 1695-1705 |
| Number of pages | 11 |
| Journal | Psychological Medicine |
| Volume | 50 |
| Issue number | 10 |
| Early online date | 22 Jul 2019 |
| DOIs | |
| Publication status | Published - Jul 2020 |
Funding
Acknowledgements. This work was funded by the Netherlands Organization for Scientific Research (NWO Brain & Cognition 433-09-228) and supported by strategic funding from The University of Queensland and from the Children\u2019s Hospital Foundation. The analyses were carried out on the Genetic Cluster Computer, which is financed by the Netherlands Scientific Organization (NWO; 480-05-003), by Vrije Universiteit Amsterdam and by the Dutch Brain Foundation and is hosted by the Dutch National Computing and Networking Services (SurfSARA). This research has been conducted using summary statistics data available via the website of the Psychiatric Genomics Consortium. We thank the participants and researchers who contributed and collected the data. This work was funded by the Netherlands Organization for Scientific Research (NWO Brain & Cognition 433-09-228) and supported by strategic funding from The University of Queensland and from the Children's Hospital Foundation.
| Funders | Funder number |
|---|---|
| Netherlands Organization for Scientific Research | |
| Royal Children's Hospital Foundation | |
| Netherlands Scientific Organization | |
| Vrije Universiteit Amsterdam | |
| Dutch National Computing and Networking Services | |
| University of Queensland | |
| Dutch Brain Foundation | |
| Children’s Hospital Foundation | |
| Not added | 480-05-003, 433-09-228 |
