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

Date

2019-06-01

Author

Guloksuz, Sinan
Pries, Lotta-Katrin
Delespaul, Philippe
Kenis, Gunter
Luykx, Jurjen J.
Lin, Bochao D.
Richards, Alexander L.
Akdede, Berna
Binbay, Tolga
ALTINYAZAR, VESİLE
Yalincetin, Berna
Gumus-Akay, Guvem
Cihan, Burçin
Soygur, Haldun
ULAŞ, HALİS
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
ALPTEKİN, KÖKSAL
SAKA, MERAM CAN
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

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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.

Subject Keywords

Phychiatric Mental Health, Psychiatry and Mental health

URI

https://hdl.handle.net/11511/56660

Journal

WORLD PSYCHIATRY

DOI

https://doi.org/10.1002/wps.20629

Collections

Department of Psychology, Article

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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.