Classification of schizophrenia, bipolar disorder and major depressive disorder with comorbid traits and deep learning algorithms
Many psychiatric disorders share genetic liabilities, but whether these shared liabilities can be utilized to classify and differentiate psychiatric disorders remains unclear. In this study, we use polygenic risk scores (PRSs) of 42 traits comorbid with schizophrenia (SCZ), bipolar disorder (BIP), and major depressive disorder (MDD) to evaluate their utilities. We found that combining target specific PRS with PRSs of comorbid traits can improve the classification of the target disorders. Importantly, without inclusion of PRSs from targeted disorders, we can still classify SCZ (accuracy 0.710 ± 0.008, AUC 0.789 ± 0.011), BIP (accuracy 0.782 ± 0.006, AUC 0.852 ± 0.004), and MDD (accuracy 0.753 ± 0.019, AUC 0.822 ± 0.010). Furthermore, PRSs from comorbid traits alone can effectively differentiate unaffected controls and patients with SCZ, BIP, and MDD (accuracy 0.861 ± 0.003, AUC 0.961 ± 0.041). Our results demonstrate that shared liabilities can be used effectively to improve the classification and differentiation of these disorders. The finding that PRSs from comorbid traits alone can classify and differentiate SCZ, BIP and MDD reasonably well implies that a majority of the risk variants composing target PRSs are shared with comorbid traits. Overall, our results suggest that a data-driven approach may be feasible to classify and differentiate these disorders.
Authors
- Shizhong Han (ORCID: https://orcid.org/0000-0002-5114-6742)
- Zhongming Zhao (ORCID: https://orcid.org/0000-0002-3477-0914)
- Yimei Lu
- Joan Manuel Cue (ORCID: https://orcid.org/0000-0002-6803-8465)
- Jingchun Chen (ORCID: https://orcid.org/0000-0001-9408-0117)
- Daniel R. Weinberger (ORCID: https://orcid.org/0000-0003-2409-2969)
- Mira Han (ORCID: https://orcid.org/0000-0002-0488-1170)
- Vishwajit L. Nimgaonkar (ORCID: https://orcid.org/0000-0001-8485-5927)
- Xiangning Chen (ORCID: https://orcid.org/0000-0001-9575-9447)
Institutions
- University of Nevada, Las Vegas (US)
- Johns Hopkins University (US)
- University of Pittsburgh (US)
- Johns Hopkins Medicine (US)
- Lieber Institute for Brain Development (US)
- The University of Texas Health Science Center (US)
Publication Details
- Journal
- Schizophrenia
- Published
- 2025-02-05
- DOI
- https://doi.org/10.1038/s41537-025-00564-7
- Citations
- 5
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 9.09
Funders
- Eli Lilly and Company
- University of Pennsylvania
- Emory University
- Northwestern University
- Louisiana State University
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Karolinska Institutet
- Vetenskapsrådet
- National Institutes of Health
- School of Medicine, Emory University
- Stanley Center for Psychiatric Research, Broad Institute
- National Institute of Mental Health
- National Institute of General Medical Sciences
- U.S. National Library of Medicine