Chen Xiangning, Lu Yimei, Cue Joan Manuel, Han Mira V, Nimgaonkar Vishwajit L, Weinberger Daniel R, Han Shizhong, Zhao Zhongming, Chen Jingchun
Center for Precision Medicine, McWilliams School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Department of Bioinformatics and Systems Medicine, McWilliams School of Biomedical Informatics, University of Texas Health Science Center at Houton, Houston, Texas, USA.
Schizophrenia (Heidelb). 2025 Feb 5;11(1):14. doi: 10.1038/s41537-025-00564-7.
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.
许多精神疾病存在共同的遗传易感性,但这些共同的易感性能否用于对精神疾病进行分类和鉴别仍不清楚。在本研究中,我们使用了与精神分裂症(SCZ)、双相情感障碍(BIP)和重度抑郁症(MDD)共病的42种性状的多基因风险评分(PRSs)来评估它们的效用。我们发现,将目标特异性PRS与共病性状的PRS相结合可以改善目标疾病的分类。重要的是,在不纳入目标疾病的PRS的情况下,我们仍然可以对SCZ(准确率0.710±0.008,AUC 0.789±0.011)、BIP(准确率0.782±0.006,AUC 0.852±0.004)和MDD(准确率0.753±0.019,AUC 0.822±0.010)进行分类。此外,仅共病性状的PRS就能有效区分未受影响的对照者与SCZ、BIP和MDD患者(准确率0.861±0.003,AUC 0.961±0.041)。我们的结果表明,共同的易感性可以有效地用于改善这些疾病的分类和鉴别。仅共病性状的PRS就能较好地对SCZ、BIP和MDD进行分类和鉴别,这一发现意味着构成目标PRS的大多数风险变异与共病性状是共享的。总体而言,我们的结果表明,一种数据驱动的方法可能对这些疾病的分类和鉴别是可行的。