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Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study

Aas, Monica and Alameda, Luis and Di Forti, Marta and Quattrone, Diego and Dazzan, Paola and Trotta, Antonella and Ferraro, Laura and Rodriguez, Victoria and Vassos, Evangelos and Sham, Pak and Tripoli, Giada and Cascia, Caterina La and Barbera, Daniele La and Tarricone, Ilaria and Muratori, Roberto and Berardi, Domenico and Lasalvia, Antonio and Tosato, Sarah and Szöke, Andrei and Llorca, Pierre-Michel and Arango, Celso and Tortelli, Andrea and de Haan, Lieuwe and Velthorst, Eva and Bobes, Julio and Bernardo, Miguel and Sanjuán, Julio and Santos, Jose Luis and Arrojo, Manuel and Del-Ben, Cristina Marta and Menezes, Paulo Rossi and Selten, Jean-Paul and Jones, Peter B and Jongsma, Hannah E and Kirkbride, James B and Rutten, Bart PF and van Os, Jim and Gayer-Anderson, Charlotte and Murray, Robin M and Morgan, Craig (2021) 'Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study.' Psychological Medicine. pp. 1-9. ISSN 0033-2917

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Background A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. Methods We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case–control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS − ORexposure − ORPRS + 1] with adjustment for potential confounders. Results There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) −1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI −6.25 to 20.88). Conclusions Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.

Item Type: Article
Uncontrolled Keywords: Childhood trauma; first-episode psychosis; interaction contrast ratio; polygenic risk; schizophrenia; synergistic effects
Divisions: Faculty of Science and Health
Faculty of Science and Health > Health and Social Care, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 24 Feb 2022 21:32
Last Modified: 13 Jun 2022 10:04

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