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

• DOI: 10.1017/s0033291721003664
• Publication Date: 2021-09-29T12:41:12Z
• Authors: 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 Llorca; Celso Arango; Andrea Tortelli; Lieuwe de Haan; Eva Velthorst; Julio Bobes; Miguel Bernardo; Julio Sanjuán; Jose Luis Santos; Manuel Arrojo; Cristina Marta De...; Paulo Rossi Menezes; Jean-Paul Selten; Peter B. Jones; Hannah E. Jongsma; James B. Kirkbride; Bart P. F. Rutten; Jim van Os; Charlotte Gayer-A...; Robin M. Murray; Craig Morgan
• Keywords: CTQ tree; Polygenic risk score

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