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. 2019 Jun;18(2):173-182.
doi: 10.1002/wps.20629.

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

Sinan Guloksuz  1   2 , Lotta-Katrin Pries  1 , Philippe Delespaul  1 , Gunter Kenis  1 , Jurjen J Luykx  3   4   5 , Bochao D Lin  4 , Alexander L Richards  6 , Berna Akdede  7 , Tolga Binbay  7 , Vesile Altınyazar  8 , Berna Yalınçetin  9 , Güvem Gümüş-Akay  10 , Burçin Cihan  11 , Haldun Soygür  12 , Halis Ulaş  13 , EylemŞahin Cankurtaran  14 , Semra Ulusoy Kaymak  15 , Marina M Mihaljevic  16   17 , Sanja Andric Petrovic  17 , Tijana Mirjanic  18 , Miguel Bernardo  19   20   21 , Bibiana Cabrera  19   20   21 , Julio Bobes  21   22   23   24 , Pilar A Saiz  21   22   23   24 , María Paz García-Portilla  21   22   23   24 , Julio Sanjuan  21   25 , Eduardo J Aguilar  21   25 , José Luis Santos  21   26 , Estela Jiménez-López  21   27 , Manuel Arrojo  28 , Angel Carracedo  29 , Gonzalo López  21   30 , Javier González-Peñas  21   30 , Mara Parellada  21   30 , Nadja P Maric  16   17 , Cem Atbaşog Lu  31 , Alp Ucok  32 , Köksal Alptekin  7 , Meram Can Saka  31 ; Genetic Risk and Outcome of Psychosis (GROUP) investigators; Celso Arango  21   30 , Michael O'Donovan  6 , Bart P F Rutten  1 , Jim van Os  1   3   33
Collaborators, Affiliations

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

Sinan Guloksuz et al. World Psychiatry. 2019 Jun.

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; bullying; cannabis; childhood trauma; environment; gene-environment interaction; genetics; polygenic risk; psychosis.

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Figures

Figure 1
Figure 1
Additive effects of cannabis use, emotional abuse, sexual abuse, emotional neglect and bullying on the association between the polygenic risk score for schizophrenia, 75% cut‐point (PRS) and case‐control status, adjusted for sex, age and ten principal components; RERI – relative excess risk due to interaction
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