We investigated the predictive value of polygenic risk scores (PRS) derived from the schizophrenia GWAS (Trubetskoy et al., 2022) for phenotypic traits of bipolar disorder type-I (BP-I) in 1878 BP-I cases and 2751 controls from Romania and UK. We used PRSice-v2.3.3 and PRS-CS for computing SCZ3-PRS for testing the predictive power of SCZ3-PRS alone and in combination with clinical variables for several BP-I subphenotypes and for pathway analysis. Non-linear predictive models were also used. SCZ3-PRS significantly predicted psychosis, incongruent and congruent psychosis, general age-of-onset (AO) of BP-I, AO-depression, AO-Mania, rapid cycling in univariate regressions. A negative correlation between the number of depressive episodes and psychosis, mainly incongruent and an inverse relationship between increased SCZ3-SNP loading and BP-I-rapid cycling were observed. In random forest models comparing the predictive power of SCZ3-PRS alone and in combination with nine clinical variables, the best predictions were provided by combinations of SCZ3-PRS-CS and clinical variables closely followed by models containing only clinical variables. SCZ3-PRS performed worst. Twenty-two significant pathways underlying psychosis were identified. The combined RO-UK sample had a certain degree of heterogeneity of the BP-I severity: only the RO sample and partially the UK sample included hospitalized BP-I cases. The hospitalization is an indicator of illness severity. Not all UK subjects had complete subphenotype information. Our study shows that the SCZ3-PRS have a modest clinical value for predicting phenotypic traits of BP-I. For clinical use their best performance is in combination with clinical variables.

中文翻译：

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精神分裂症多基因风险评分、临床变量和遗传途径作为 I 型双相情感障碍表型特征的预测因子

我们研究了源自精神分裂症 GWAS（Trubetskoy 等人，2022）的多基因风险评分 (PRS) 对来自罗马尼亚的 1878 名 BP-I 病例和 2751 名对照者中 I 型双相情感障碍 (BP-I) 表型特征的预测价值和英国。我们使用 PRSice-v2.3.3 和 PRS-CS 来计算 SCZ3-PRS，以测试 SCZ3-PRS 单独的预测能力以及与几种 BP-I 亚表型的临床变量相结合的预测能力以及路径分析。还使用了非线性预测模型。 SCZ3-PRS 显着预测精神病、不一致和一致精神病、BP-I 的一般发病年龄 (AO)、AO 抑郁、AO 躁狂、单变量回归中的快速循环。观察到抑郁发作次数与精神病之间呈负相关，主要是 SCZ3-SNP 负载增加与 BP-I-快速循环之间不一致且呈反比关系。在比较 SCZ3-PRS 单独和与九个临床变量组合的预测能力的随机森林模型中，SCZ3-PRS-CS 和临床变量的组合提供了最佳预测，紧随其后的是仅包含临床变量的模型。 SCZ3-PRS 表现最差。确定了精神病的二十二条重要途径。 RO-UK 合并样本的 BP-I 严重程度存在一定程度的异质性：仅 RO 样本和部分 UK 样本包括住院 BP-I 病例。住院情况是疾病严重程度的一个指标。并非所有英国受试者都有完整的亚表型信息。我们的研究表明 SCZ3-PRS 对于预测 BP-I 表型特征具有一定的临床价值。对于临床使用，它们的最佳性能是与临床变量相结合。