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. 2020 Jul 8;46(4):1019-1025.
doi: 10.1093/schbul/sbaa012.

Examining Gene-Environment Interactions Using Aggregate Scores in a First-Episode Psychosis Cohort

Sergi Mas  1   2   3 , Daniel Boloc  4 , Natalia Rodríguez  1   2   3 , Gisela Mezquida  1   2   3   5 , Silvia Amoretti  2   3   5 , Manuel J Cuesta  6   7 , Javier González-Peñas  8 , Alicia García-Alcón  8 , Antonio Lobo  9 , Ana González-Pinto  2   10   11   12 , Iluminada Corripio  13   14 , Eduard Vieta  3   15   16 , Josefina Castro-Fornieles  17 , Anna Mané  18   19 , Jeronimo Saiz-Ruiz  20 , Patricia Gassó  1   2   3 , Miquel Bioque  5 , Miquel Bernardo  3   4   21   22 ; PEPs Group
Affiliations

Examining Gene-Environment Interactions Using Aggregate Scores in a First-Episode Psychosis Cohort

Sergi Mas et al. Schizophr Bull. .

Abstract

Gene-environment (GxE) interactions have been related to psychosis spectrum disorders, involving multiple common genetic variants in multiple genes with very small effect sizes, and several environmental factors that constitute a dense network of exposures named the exposome. Here, we aimed to analyze GxE in a cohort of 310 first-episode psychotic (FEP) and 236 healthy controls, by using aggregate scores estimated in large populations such as the polygenic risk score for schizophrenia and (PRS-SCZ) and the Maudsley environmental risk score (ERS). In contrast to previous findings, in our study, the PRS-SCZ did not discriminate cases from controls, but the ERS score explained a similar percentage of the variance as in other studies using similar approaches. Our study supports a positive additive interaction, indicating synergy between genetic susceptibility to schizophrenia (PRS-SCZ dichotomized according to the highest quartile distribution of the control population) and the exposome (ERS > 75% of the controls). This additive interaction showed genetic and environmental dose dependence. Our study shows that the use of aggregate scores derived from large and powered studies instead of statistics derived from specific sample characteristics is a powerful tool for the study of the effects of GxE on the risk of psychotic spectrum disorders. In conclusion, by using a genetic risk score and an ERS we have provided further evidence for the role of GxE in psychosis.

Keywords: environmental risk score; exposome; genetics; polygenic risk score; psychosis.

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