Grigoroiu-Serbanescu, Maria; Van der Veen, Tracey; Bigdeli, Tim; Herms, Stefan; Diaconu, Carmen C; Neagu, Ana Iulia; Bass, Nicholas; ... McQuillin, Andrew; + view all Grigoroiu-Serbanescu, Maria; Van der Veen, Tracey; Bigdeli, Tim; Herms, Stefan; Diaconu, Carmen C; Neagu, Ana Iulia; Bass, Nicholas; Thygesen, Johan; Forstner, Andreas J; Nöthen, Markus M; McQuillin, Andrew; - view fewer (2024) Schizophrenia polygenic risk scores, clinical variables and genetic pathways as predictors of phenotypic traits of bipolar I disorder. Journal of Affective Disorders , 356 pp. 507-518. 10.1016/j.jad.2024.04.066.

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Abstract

AIM: We investigated the predictive value of polygenic risk scores (PRS) derived from the schizophrenia GWAS (Trubetskoy et al., 2022) (SCZ3) for phenotypic traits of bipolar disorder type-I (BP-I) in 1878 BP-I cases and 2751 controls from Romania and UK. METHODS: 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. RESULTS: 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. LIMITATIONS: 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. CONCLUSION: 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.

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