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https://oxfordhealth-nhs.archive.knowledgearc.net/handle/123456789/97
Title: | Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression |
Authors: | Tunbridge, Elizabeth Harrison, Paul J |
Keywords: | Genetics Mental Disorders Bipolar Disorder Attention Deficit Hyperactivity Disorder (ADHD) |
Issue Date: | 2018 |
Citation: | Strawbridge, R; Ward, Joey; Lyall, Laura; Tunbridge, Elizabeth; Cullen, Breda; Graham, Nicholas; Ferguson, AGenetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expressionmy; Johnston, Keira; Lyall, Donald; MacKay,Daniel; Cavanagh, Jonathan; Howard, David; Adams, Mark; Deary, Ian; Escott-Price, Valentina; O'Donovan, Michael; McIntosh, Andrew; Bailey, Mark; Bell, Jill; Harrison, Paul; Smith, Daniel. Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression. Translational Pyschiatry (8) 2018, 178 el; |
Abstract: | Risk-taking behaviour is an important component of several psychiatric disorders, including attention-deficit hyperactivity disorder, schizophrenia and bipolar disorder. Previously, two genetic loci have been associated with self-reported risk taking and significant genetic overlap with psychiatric disorders was identified within a subsample of UK Biobank. Using the white British participants of the full UK Biobank cohort (nā=ā83,677 risk takers versus 244,662 controls) for our primary analysis, we conducted a genome-wide association study of self-reported risk-taking behaviour. In secondary analyses, we assessed sex-specific effects, trans-ethnic heterogeneity and genetic overlap with psychiatric traits. We also investigated the impact of risk-taking-associated SNPs on both gene expression and structural brain imaging. We identified 10 independent loci for risk-taking behaviour, of which eight were novel and two replicated previous findings. In addition, we found two further sex-specific risk-taking loci. There were strong positive genetic correlations between risk-taking and attention-deficit hyperactivity disorder, bipolar disorder and schizophrenia. Index genetic variants demonstrated effects generally consistent with the discovery analysis in individuals of non-British White, South Asian, African-Caribbean or mixed ethnicity. Polygenic risk scores comprising alleles associated with increased risk taking were associated with lower white matter integrity. Genotype-specific expression pattern analyses highlighted DPYSL5, CGREF1 and C15orf59 as plausible candidate genes. Overall, our findings substantially advance our understanding of the biology of risk-taking behaviour, including the possibility of sex-specific contributions, and reveal consistency across ethnicities. We further highlight several putative novel candidate genes, which may mediate these genetic effects. |
Description: | https://doi.org/10.1038/s41398-018-0236-1 This is an Open Access article under the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). Eligible users can access the full text via NHS OpenAthens at [https://www.nature.com/articles/s41398-018-0236-1]. |
URI: | https://oxfordhealth-nhs.archive.knowledgearc.net/handle/123456789/97 |
Appears in Collections: | Genetics |
Files in This Item:
File | Description | Size | Format | |
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Strawbridge_Genetic_2018.pdf | Main Article | 1.44 MB | Adobe PDF | View/Open |
Genetics_Supplementary File1.pdf | Supplementary File 1 | 80.25 kB | Adobe PDF | View/Open |
Genetics_Supplementary Figure2.pdf | Supplementary File 2 | 1.05 MB | Adobe PDF | View/Open |
Genetics_Supplementary Figure3.pdf | Supplementary File 3 | 994.17 kB | Adobe PDF | View/Open |
Genetics_Supplementary Figure4.pdf | 513.27 kB | Adobe PDF | View/Open | |
Genetics_Supplementary Figure5.pdf | Supplementary File 5 | 950.75 kB | Adobe PDF | View/Open |
Supplementary Table 2.xlsx | SupplementaryTable 2 | 8.82 kB | Microsoft Excel XML | View/Open |
Supplementary Table 3.xlsx | Supplementary Table 3 | 17.01 kB | Microsoft Excel XML | View/Open |
Supplementary Table 4.docx | Supplementary Table 4 | 13.28 kB | Microsoft Word XML | View/Open |
Supplementary Table 5.docx | Supplementary Table 5 | 17.54 kB | Microsoft Word XML | View/Open |
Supplementary Table 6.docx | Supplementary Table 6 | 20.23 kB | Microsoft Word XML | View/Open |
Suplementary Table 7.xlsx | Supplementary Table 7 | 10.68 kB | Microsoft Excel XML | View/Open |
Supplementary Table 8.docx | Supplementary Table 8 | 16.6 kB | Microsoft Word XML | View/Open |
Supplementary Table 9.docx | Supplementary Table 8 | 14.91 kB | Microsoft Word XML | View/Open |
Supplementary Table 10.docx | Supplementary Table 10 | 14.08 kB | Microsoft Word XML | View/Open |
Supplementary Table 11.xlsx | Supplementary Table 11 | 11.3 kB | Microsoft Excel XML | View/Open |
Supplementary Table 12.xlsx | Supplementary Table 12 | 10 kB | Microsoft Excel XML | View/Open |
Supplementary Table 13.xlsx | Supplementary Table 13 | 9.47 kB | Microsoft Excel XML | View/Open |
Supplementary Table 14.xlsx | Supplementary Table 14 | 12.58 kB | Microsoft Excel XML | View/Open |
Supplementary Table 15.xlsx | Supplementary Table 15 | 12.25 kB | Microsoft Excel XML | View/Open |
Supplementary Table 16.docx | Supplementary Table 16 | 22.98 kB | Microsoft Word XML | View/Open |
Supplementary Table 17.docx | Supplementary Table 17 | 17.7 kB | Microsoft Word XML | View/Open |
Supplementary Table 18.docx | Supplementary Table 18 | 46.01 kB | Microsoft Word XML | View/Open |
Supplementary Table 19.xlsx | Supplementary Table 19 | 10.88 kB | Microsoft Excel XML | View/Open |
Supplementary Table 20.docx | Supplementary Table 20 | 15.77 kB | Microsoft Word XML | View/Open |
Supplementary Table 21.docx | Supplementary Table 21 | 50.04 kB | Microsoft Word XML | View/Open |
Supplementary Table 22.xlsx | Supplementary Table 22 | 11.11 kB | Microsoft Excel XML | View/Open |
Supplementary Table 23.xlsx | Supplementary Table 23 | 9.27 kB | Microsoft Excel XML | View/Open |
Supplementary Table 24.xlsx | Supplementary Table 24 | 9.77 kB | Microsoft Excel XML | View/Open |
Supplementary Table 25.xlsx | Supplementary Table 25 | 12.26 kB | Microsoft Excel XML | View/Open |
Supplementary Table 26.xlsx | Supplementary Table 26 | 12.48 kB | Microsoft Excel XML | View/Open |
Genetics_Supplementary Figure6.pdf | Genetics Supplementary File 6 | 4.46 MB | Adobe PDF | View/Open |
Supplementary Table 1.xlsx | Supplementary Table 1 | 10.18 kB | Microsoft Excel XML | View/Open |
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