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Use of multiple Polygenic Risk Scores for distinguishing Schizophrenia-spectrum disorder and Affective psychosis categories; the EUGEI study [article]

Victoria Rodriguez, Luis Alameda, Diego Quattrone, Giada Tripoli, Charlotte Gayer-Anderson, Edoardo Spinazzola, Giulia Trotta, Hannah Jongsma, Simona Stilo, Caterina La Cascia, Laura Ferraro, Daniele La Barbera (+24 others)
2021 medRxiv   pre-print

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Schizophrenia (SZ), Bipolar Disorder (BD) and Depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUGEI case-control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can
more » ... riminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD). Participants (573 cases, 1005 controls) of european ancestry from 17 sites as part of the EUGEI study were successfully genotyped following standard quality control procedures. Using standardised PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons. In case-control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case-case comparison, both PRS-SZ (OR=0.7, 95 %CI 0.53-0.92) and PRS-D (OR=1.29, 95%CI 1.05-1.6) differentiated global AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR=2.38, 95%CI 1.32-4.29). Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards potential usefulness of PRSs for diagnostic prediction in specific populations such as high-risk or early psychosis phases.
doi:10.1101/2021.03.31.21254574 fatcat:xu5f2dwk4rh5dlaagyr3xmap4y
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Victoria Rodriguez, Luis Alameda, Diego Quattrone, Giada Tripoli, Charlotte Gayer-Anderson, Edoardo Spinazzola, Giulia Trotta, Hannah Jongsma, Simona Stilo, Caterina La Cascia, Laura Ferraro, Daniele La Barbera, Antonio Lasalvia, Sarah Tosato, Ilaria Tarricone, Elena Bonora, Stephane Jamain, Jean-Paul Selten, Eva Velthorst, Lieuwe de Haan, Pierre-Michel Llorca, Manuel Arrojo, Julio Bobes, Miguel Bernardo, Celso Arango, James Kirkbride, Peter B Jones, Bart P Rutten, Alexander Richards, Pak C Sham, Michael O'Donovan, Jim Van Os, Craig Morgan, Marta Di Forti, Robin M Murray, Evangelos Vassos. "Use of multiple Polygenic Risk Scores for distinguishing Schizophrenia-spectrum disorder and Affective psychosis categories; the EUGEI study." medRxiv (2021)