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

Guloksuz, Sinan
Pries, Lotta-Katrin
Delespaul, Philippe
Kenis, Gunter
Luykx, Jurjen J.
Lin, Bochao D.
Richards, Alexander L.
Akdede, Berna
Binbay, Tolga
Yalincetin, Berna
Gumus-Akay, Guvem
Cihan, Burçin
Soygur, Haldun
Cankurtaran, Eylem Sahin
Kaymak, Semra Ulusoy
Mihaljevic, Marina M.
Petrovic, Sanja Andric
Mirjanic, Tijana
Bernardo, Miguel
Cabrera, Bibiana
Bobes, Julio
Saiz, Pilar A.
Paz Garcia-Portilla, Maria
Sanjuan, Julio
Aguilar, Eduardo J.
Luis Santos, Jose
Jimenez-Lopez, Estela
Arrojo, Manuel
Carracedo, Angel
Lopez, Gonzalo
Gonzalez-Penas, Javier
Parellada, Mara
Maric, Nadja P.
Atbasoglu, Cem
Ucok, Alp
Arango, Celso
O'Donovan, Michael
Rutten, Bart P. F.
van Os, Jim
Alizadeh, Behrooz Z.
van Amelsvoort, Therese
van Beveren, Nico J.
Bruggeman, Richard
Cahn, Wiepke
de Haan, Lieuwe
Myin-Germeys, Inez
van Winkel, Ruud
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.


Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene-environment interaction. The EUGEI study
van Os, Jim; et. al. (Cambridge University Press (CUP), 2020-08-01)
Background First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes. Methods We conducted, using two different samples for discovery (n= 336 controls and 649 siblings of patients with psychotic disorder) and replication (n= 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other ...
Sociodemographic/clinical characteristics and risk factors associated with chronic tic disorders
Tural Hesapçioǧlu, Selma; Tural, Mustafa Kemal; KANDİL, SEMA (Turkish Association of Nervous and Mental Health, 2013-01-01)
Objective: This study aimed to investigate comorbidity, and sociodemographic and clinical characteristics in children and adolescents with Tourette's syndrome (TS) and chronic motor or vocal tic disorder (CMVTD), and to determine the predictors of tic disorders. Materials and Methods: In all, 57 children and adolescents with TS and CMVTD were compared with a control group. Data were obtained using the Yale Global Tic Severity Scale (YGTSS), Turgay DSM-IV-Based Disruptive Behavioral Disorders Screening and ...
Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway
Van Os, Jim; et. al. (2022-07-19)
Background There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation. Methods We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population s...
Autism screening questionnaire: diagnostic validity
Kazak Berument, Sibel; Lord, C; Pickles, A; Bailey, A (Royal College of Psychiatrists, 1999-11-01)
Background: Good interview and diagnostic measures for autism and other pervasive developmental disorders (PDDs) are available but there is a lack of a good screening questionnaire. Aims: To develop and test a screening questionnaire based on items in the best available diagnostic interview--the Autism Diagnostic Interview--Revised (ADI-R). Method: A 40-item scale, the Autism Screening Questionnaire (ASQ), was developed and tested on a sample of 160 individuals with PDD and 40 with non-PDD diagnoses. Res...
ARKAR, H; EKER, D (SAGE Publications, 1994-09-01)
The influence of specific psychiatric labels and types of psychopathology on various attitudes were investigated in a sample (N = 84) of visitors of patients in a Turkish hospital. Vignettes representing two types of psychopathology with and without labels were used as the stimulus material and the attitudes toward those descriptions were assessed with the use of a questionnaire. Statistical analyses showed that labels had significant influence on recognition of mental illness, social distance, expected p...
Citation Formats
S. Guloksuz et al., “Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: results from the EUGEI study,” WORLD PSYCHIATRY, pp. 173–182, 2019, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/56660.