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Multivariate GWAS of psychiatric disorders and their cardinal symptoms reveal two dimensions of cross-cutting genetic liabilities

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Mallard, T. T., Linnér, R. K., Grotzinger, A. D., Sanchez-Roige, S., Seidlitz, J., Okbay, A., e Vlaming, R., Meddens, S. F. W., Bipolar Disorder Working Group of the PGC, Palmer, A. A., Davis, L. K., Tucker-Drob, E. M., Kendler, K. S., Keller, M. C., Koellinger, P. D., Harden, K. P., Gordon-Smith, Katherine ORCID: https://orcid.org/0000-0003-4083-1143, Perry, Amy ORCID: https://orcid.org/0000-0002-9381-6636 and Jones, Lisa ORCID: https://orcid.org/0000-0002-5122-8334 (2022) Multivariate GWAS of psychiatric disorders and their cardinal symptoms reveal two dimensions of cross-cutting genetic liabilities. Cell Genomics, 2 (6). p. 100140. ISSN 2666-979X

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Official URL: https://doi.org/10.1016/j.xgen.2022.100140

Abstract

Understanding which biological pathways are specific versus general across diagnostic categories and levels of symptom severity is critical to improving nosology and treatment of psychopathology. Here, we combine transdiagnostic and dimensional approaches to genetic discovery for the first time, conducting a novel multivariate genome-wide association study of eight psychiatric symptoms and disorders broadly related to mood disturbance and psychosis. We identify two transdiagnostic genetic liabilities that distinguish between common forms of psychopathology versus rarer forms of serious mental illness. Biological annotation revealed divergent genetic architectures that differentially implicated prenatal neurodevelopment and neuronal function and regulation. These findings inform psychiatric nosology and biological models of psychopathology, as they suggest that the severity of mood and psychotic symptoms present in serious mental illness may reflect a difference in kind rather than merely in degree.

Item Type:	Article
Additional Information:	This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Katherine Gordon-Smith, Amy Perry and Lisa Jones are members of the Bipolar Disorder Working Group of the Psychiatric Genomics Consortium
Uncontrolled Discrete Keywords:	psychiatric genetics, psychiatric disorders, transdiagnostic, genome-wide association study, genetic correlation, pleiotropy, genomics, neurodevelopment
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions:	College of Health, Life and Environmental Sciences > School of Allied Health and Community
Related URLs:	Publisher
Copyright Info:	© 2022 The Author(s).
Depositing User:	Katherine Gordon-Smith
Date Deposited:	22 Aug 2022 14:13
Last Modified:	25 Aug 2022 08:29
URI:	https://worc-9.eprints-hosting.org/id/eprint/12421

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