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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-01-01
|
| Series: | npj Schizophrenia |
| Online Access: | https://doi.org/10.1038/s41537-020-00131-2 |
| _version_ | 1797430182840107008 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T09:23:56Z |
| format | Article |
| id | doaj.art-4c8f1d760fe84399aa07a9d026bfa8f1 |
| institution | Directory Open Access Journal |
| issn | 2334-265X |
| language | English |
| last_indexed | 2024-03-09T09:23:56Z |
| publishDate | 2021-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Schizophrenia |
| spelling | doaj.art-4c8f1d760fe84399aa07a9d026bfa8f12023-12-02T06:31:51ZengNature Portfolionpj Schizophrenia2334-265X2021-01-01711910.1038/s41537-020-00131-2Investigating the effects of genetic risk of schizophrenia on behavioural traitsAdam Socrates0Jessye Maxwell1Kylie P. Glanville2Marta Di Forti3Robin M. Murray4Evangelos Vassos5Paul F. O’Reilly6SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonSGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonSGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonSGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonInstitute of Psychiatry, Psychology and Neuroscience, King’s College LondonSGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonSGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonAbstract 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.https://doi.org/10.1038/s41537-020-00131-2 |
| spellingShingle | 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 npj Schizophrenia |
| title | 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_short | Investigating the effects of genetic risk of schizophrenia on behavioural traits |
| title_sort | investigating the effects of genetic risk of schizophrenia on behavioural traits |
| url | https://doi.org/10.1038/s41537-020-00131-2 |
| work_keys_str_mv | AT adamsocrates investigatingtheeffectsofgeneticriskofschizophreniaonbehaviouraltraits AT jessyemaxwell investigatingtheeffectsofgeneticriskofschizophreniaonbehaviouraltraits AT kyliepglanville investigatingtheeffectsofgeneticriskofschizophreniaonbehaviouraltraits AT martadiforti investigatingtheeffectsofgeneticriskofschizophreniaonbehaviouraltraits AT robinmmurray investigatingtheeffectsofgeneticriskofschizophreniaonbehaviouraltraits AT evangelosvassos investigatingtheeffectsofgeneticriskofschizophreniaonbehaviouraltraits AT paulforeilly investigatingtheeffectsofgeneticriskofschizophreniaonbehaviouraltraits |