Investigating the effects of genetic risk of schizophrenia on behavioural traits

Abstract To characterise the trait-effects of increased genetic risk for schizophrenia, and highlight potential risk mediators, we test the association between schizophrenia polygenic risk scores (PRSs) and 529 behavioural traits (personality, psychological, lifestyle, nutritional) in the UK Biobank...

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Autores principales:	Adam Socrates, Jessye Maxwell, Kylie P. Glanville, Marta Di Forti, Robin M. Murray, Evangelos Vassos, Paul F. O’Reilly
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Psychiatry RC435-571
Acceso en línea:	https://doaj.org/article/4c8f1d760fe84399aa07a9d026bfa8f1
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spelling	oai:doaj.org-article:4c8f1d760fe84399aa07a9d026bfa8f12021-12-02T13:48:40ZInvestigating the effects of genetic risk of schizophrenia on behavioural traits10.1038/s41537-020-00131-22334-265Xhttps://doaj.org/article/4c8f1d760fe84399aa07a9d026bfa8f12021-01-01T00:00:00Zhttps://doi.org/10.1038/s41537-020-00131-2https://doaj.org/toc/2334-265XAbstract To characterise the trait-effects of increased genetic risk for schizophrenia, and highlight potential risk mediators, we test the association between schizophrenia polygenic risk scores (PRSs) and 529 behavioural traits (personality, psychological, lifestyle, nutritional) in the UK Biobank. Our primary analysis is performed on individuals aged 38–71 with no history of schizophrenia or related disorders, allowing us to report the effects of schizophrenia genetic risk in the sub-clinical general population. Higher schizophrenia PRSs were associated with a range of traits, including lower verbal-numerical reasoning (P = 6 × 10–61), higher nervous feelings (P = 1 × 10−46) and higher self-reported risk-taking (P = 3 × 10−38). We follow-up the risk-taking association, hypothesising that the association may be due to a genetic propensity for risk-taking leading to greater migration, urbanicity or drug-taking — reported environmental risk factors for schizophrenia, and all positively associated with risk-taking in these data. Next, to identify potential disorder or medication effects, we compare the PRS–trait associations in the general population to the trait values in 599 medicated and non-medicated individuals diagnosed with schizophrenia in the biobank. This analysis highlights, for example, levels of BMI, physical activity and risk-taking in cases in the opposite directions than expected from the PRS–trait associations in the general population. Our analyses offer simple yet potentially revealing insights into the possible causes of observed trait–disorder associations, which can complement approaches such as Mendelian Randomisation. While we urge caution in causal interpretations in PRS cross-trait studies that are highly powered to detect weak horizontal pleiotropy or population structure, we propose that well-designed polygenic score analyses have the potential to highlight modifiable risk factors that lie on the path between genetic risk and disorder.Adam SocratesJessye MaxwellKylie P. GlanvilleMarta Di FortiRobin M. MurrayEvangelos VassosPaul F. O’ReillyNature PortfolioarticlePsychiatryRC435-571ENnpj Schizophrenia, Vol 7, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Psychiatry RC435-571
spellingShingle	Psychiatry RC435-571 Adam Socrates Jessye Maxwell Kylie P. Glanville Marta Di Forti Robin M. Murray Evangelos Vassos Paul F. O’Reilly Investigating the effects of genetic risk of schizophrenia on behavioural traits
description	Abstract To characterise the trait-effects of increased genetic risk for schizophrenia, and highlight potential risk mediators, we test the association between schizophrenia polygenic risk scores (PRSs) and 529 behavioural traits (personality, psychological, lifestyle, nutritional) in the UK Biobank. Our primary analysis is performed on individuals aged 38–71 with no history of schizophrenia or related disorders, allowing us to report the effects of schizophrenia genetic risk in the sub-clinical general population. Higher schizophrenia PRSs were associated with a range of traits, including lower verbal-numerical reasoning (P = 6 × 10–61), higher nervous feelings (P = 1 × 10−46) and higher self-reported risk-taking (P = 3 × 10−38). We follow-up the risk-taking association, hypothesising that the association may be due to a genetic propensity for risk-taking leading to greater migration, urbanicity or drug-taking — reported environmental risk factors for schizophrenia, and all positively associated with risk-taking in these data. Next, to identify potential disorder or medication effects, we compare the PRS–trait associations in the general population to the trait values in 599 medicated and non-medicated individuals diagnosed with schizophrenia in the biobank. This analysis highlights, for example, levels of BMI, physical activity and risk-taking in cases in the opposite directions than expected from the PRS–trait associations in the general population. Our analyses offer simple yet potentially revealing insights into the possible causes of observed trait–disorder associations, which can complement approaches such as Mendelian Randomisation. While we urge caution in causal interpretations in PRS cross-trait studies that are highly powered to detect weak horizontal pleiotropy or population structure, we propose that well-designed polygenic score analyses have the potential to highlight modifiable risk factors that lie on the path between genetic risk and disorder.
format	article
author	Adam Socrates Jessye Maxwell Kylie P. Glanville Marta Di Forti Robin M. Murray Evangelos Vassos Paul F. O’Reilly
author_facet	Adam Socrates Jessye Maxwell Kylie P. Glanville Marta Di Forti Robin M. Murray Evangelos Vassos Paul F. O’Reilly
author_sort	Adam Socrates
title	Investigating the effects of genetic risk of schizophrenia on behavioural traits
title_short	Investigating the effects of genetic risk of schizophrenia on behavioural traits
title_full	Investigating the effects of genetic risk of schizophrenia on behavioural traits
title_fullStr	Investigating the effects of genetic risk of schizophrenia on behavioural traits
title_full_unstemmed	Investigating the effects of genetic risk of schizophrenia on behavioural traits
title_sort	investigating the effects of genetic risk of schizophrenia on behavioural traits
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4c8f1d760fe84399aa07a9d026bfa8f1
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Investigating the effects of genetic risk of schizophrenia on behavioural traits

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