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

Monica Aas, Luis Alameda, Marta Di Forti, Diego Quattrone, Paola Dazzan, Antonella Trotta, Laura Ferraro, Victoria Rodriguez, Evangelos Vassos, Pak Sham, Giada Tripoli, Caterina La Cascia, Daniele La Barbera, Ilaria Tarricone, Roberto Muratori, Domenico Berardi, Antonio Lasalvia, Sarah Tosato, Andrei Szöke, Pierre Michel LlorcaCelso Arango, Andrea Tortelli, Lieuwe De Haan, Eva Velthorst, Julio Bobes, Miguel Bernardo, Julio Sanjuán, Jose Luis Santos, Manuel Arrojo, Cristina Marta Del-Ben, Paulo Rossi Menezes, Jean Paul Selten, Peter B. Jones, Hannah E. Jongsma, James B. Kirkbride, Bart P.F. Rutten, Jim Van Os, Charlotte Gayer-Anderson, Robin M. Murray, Craig Morgan

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Abstract

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.

Original languageEnglish
JournalPsychological Medicine
DOIs
StateAccepted/In press - 2021

Keywords

  • Childhood trauma
  • first-episode psychosis
  • interaction contrast ratio
  • polygenic risk
  • schizophrenia
  • synergistic effects

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