@article{9302ee8fffdd486a9c051850ba7a7e70,
title = "Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: results from the EUGEI study",
abstract = "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.",
keywords = "Schizophrenia, psychosis, genetics, environment, gene-environment interaction, polygenic risk, childhood trauma, cannabis, bullying, CHILDHOOD TRAUMA, POLYGENIC RISK, PSYCHOSIS, ASSOCIATION, DISORDERS, HERITABILITY, RELIABILITY, VALIDATION, INSTRUMENT, IMPUTATION",
author = "Sinan Guloksuz and Lotta-Katrin Pries and Philippe Delespaul and Gunter Kenis and Luykx, {Jurjen J.} and Lin, {Bochao D.} and Richards, {Alexander L.} and Berna Akdede and Tolga Binbay and Vesile Altinyazar and Berna Yalincetin and Guvem Gumus-Akay and Burcin Cihan and Haldun Soygur and Halis Ulas and Cankurtaran, {Eylem Sahin} and Kaymak, {Semra Ulusoy} and Mihaljevic, {Marina M.} and Petrovic, {Sanja Andric} and Tijana Mirjanic and Miguel Bernardo and Bibiana Cabrera and Julio Bobes and Saiz, {Pilar A.} and {Paz Garcia-Portilla}, Maria and Julio Sanjuan and Aguilar, {Eduardo J.} and {Luis Santos}, Jose and Estela Jimenez-Lopez and Manuel Arrojo and Angel Carracedo and Gonzalo Lopez and Javier Gonzalez-Penas and Mara Parellada and Maric, {Nadja P.} and Cem Atbasoglu and Alp Ucok and Koksal Alptekin and Saka, {Meram Can} and Celso Arango and Michael O'Donovan and Rutten, {Bart P. F.} and {van Os}, Jim and Alizadeh, {Behrooz Z.} and {van Amelsvoort}, Therese and {van Beveren}, {Nico J.} and Richard Bruggeman and Wiepke Cahn and Inez Myin-Germeys and {van Winkel}, Ruud and {Genetic Risk and Outcome of Psychosis (GROUP) Investigators}",
note = "Funding Information: The EUGEI project was supported by the grant agreement HEALTH-F2-2010-241909 from the European Community{\textquoteright}s Seventh Framework Programme. The authors are grateful to the patients and their families for participating in the project. They also thank all research personnel involved in the GROUP project, in particular J. van Baaren, E. Veermans, G. Driessen, T. Driesen, E. van{\textquoteright}t Hag and J. de Nijs. All the DNA samples from Turkey were provided by the Ankara University Brain Research Center Biobank, that was supported by Ankara University Scientific Research Projects Coordination Unit (project no. 10A6055003, 2010). B.P.F. Rutten was funded by a VIDI award (no. 91718336) from the Netherlands Scientific Organization. S. Guloksuz, L.-K. Pries, B.P.F. Rutten and J. van Os contributed equally to this work. Publisher Copyright: {\textcopyright} 2019 World Psychiatric Association",
year = "2019",
month = jun,
doi = "10.1002/wps.20629",
language = "English",
volume = "18",
pages = "173--182",
journal = "World Psychiatry",
issn = "1723-8617",
publisher = "Wiley",
number = "2",
}