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Oxytocin-pathway polygenic scores for severe mental disorders and metabolic phenotypes in the UK Biobank

Abstract:
AbstractOxytocin is a neuromodulator and hormone that is typically associated with social cognition and behavior. In light of its purported effects on social cognition and behavior, research has investigated its potential as a treatment for psychiatric illnesses characterized by social dysfunction, such as schizophrenia and bipolar disorder. While the results of these trials have been mixed, more recent evidence suggests that the oxytocin system is also linked with cardiometabolic conditions for which individuals with severe mental disorders are at a higher risk for developing. To investigate whether the oxytocin system has a pleiotropic effect on the etiology of severe mental illness and cardiometabolic conditions, we explored oxytocin’s role in the shared genetic liability of schizophrenia, bipolar disorder, type-2 diabetes, and several phenotypes linked with cardiovascular disease and type 2 diabetes risk using a polygenic pathway-specific approach. Analysis of a large sample with about 480,000 individuals (UK Biobank) revealed statistically significant associations across the range of phenotypes analyzed. By comparing these effects to those of polygenic scores calculated from 100 random gene sets, we also demonstrated the specificity of many of these significant results. Altogether, our results suggest that the shared effect of oxytocin-system dysfunction could help partially explain the co-occurrence of social and cardiometabolic dysfunction in severe mental illnesses.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41398-021-01725-9

Authors

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Role:
Author
ORCID:
0000-0002-8678-3610
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Role:
Author
ORCID:
0000-0001-7968-8642
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Institution:
University of Oxford
Role:
Author
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Role:
Author
ORCID:
0000-0001-6442-1179


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Funder identifier:
10.13039/501100009708
Grant:
NFF16OC0019856
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Funder identifier:
10.13039/501100005416
Grant:
301767


Publisher:
Springer Nature [academic journals on nature.com]
Journal:
Translational Psychiatry More from this journal
Volume:
11
Issue:
1
Pages:
599-599
Article number:
599
Publication date:
2021-11-25
DOI:
EISSN:
2158-3188
ISSN:
2158-3188


Language:
English
Keywords:
Pubs id:
1222255
Local pid:
pubs:1222255
Source identifiers:
W3135624431
Deposit date:
2026-04-08
ARK identifier:
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