Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: results from the EUGEI study

Schizophrenia is a heritable complex phenotype associated with a background risk involving multiple common genetic variants of small effect and a multitude of environmental exposures. Early twin and family studies using proxy-genetic liability measures suggest gene-environment interaction in the eti...

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Detalles Bibliográficos
Autores: Guloksuz, S, Pries, LK, Delespaul, P, Kenis, G, Luykx, JJ, Lin, BCD, Richards, AL, Akdede, B, Binbay, T, Altinyazar, V, Yalincetin, B, Gumus-Akay, G, Cihan, B, Soygur, H, Ulas, H, Cankurtaran, ES, Kaymak, SU, Mihaljevic, MM, Petrovic, SA, Mirjanic, T, Bernardo, M, Cabrera, B, Bobes, J, Saiz, PA, Garcia-Portilla, MP, Sanjuan, J, Aguilar, EJ, Santos, JL, Jimenez-Lopez, E, Arrojo, M, Carracedo, A, Lopez, G, Gonzalez-Penas, J, Parellada, M, Maric, NP, Atbasoglu, C, Ucok, A, Alptekin, K, Saka, MC, Arango, C, O'Donovan, M, Rutten, BPF, van Os, J, Alizadeh, BZ, van Amelsvoort, T, van Beveren, NJ, Bruggeman, R, Cahn, W, de Haan, L, Myin-Germeys, I, van Winkel, R, Genetic Risk Outcome Psychosis
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p3742
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/3742
Access Level:acceso abierto
Palabra clave:Schizophrenia
psychosis
genetics
environment
gene-environment interaction
polygenic risk
childhood trauma
cannabis
bullying
Descripción
Sumario:Schizophrenia is a heritable complex phenotype associated with a background risk involving multiple common genetic variants of small effect and a multitude of environmental exposures. Early twin and family studies using proxy-genetic liability measures suggest gene-environment interaction in the etiology of schizophrenia spectrum disorders, but the molecular evidence is scarce. Here, by analyzing the main and joint associations of polygenic risk score for schizophrenia (PRS-SCZ) and environmental exposures in 1,699 patients with a diagnosis of schizophrenia spectrum disorders and 1,542 unrelated controls with no lifetime history of a diagnosis of those disorders, we provide further evidence for gene-environment interaction in schizophrenia. Evidence was found for additive interaction of molecular genetic risk state for schizophrenia (binary mode of PRS-SCZ above 75% of the control distribution) with the presence of lifetime regular cannabis use and exposure to early-life adversities (sexual abuse, emotional abuse, emotional neglect, and bullying), but not with the presence of hearing impairment, season of birth (winter birth), and exposure to physical abuse or physical neglect in childhood. The sensitivity analyses replacing the a priori PRS-SCZ at 75% with alternative cut-points (50% and 25%) confirmed the additive interaction. Our results suggest that the etiopathogenesis of schizophrenia involves genetic underpinnings that act by making individuals more sensitive to the effects of some environmental exposures.

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