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Polygenic contributions to performance on the Balloon Analogue Risk Task
Risky decision-making is a common, heritable endophenotype seen across many psychiatric disorders. Its underlying genetic architecture is incompletely explored. We examined behavior in the Balloon Analogue Risk Task (BART), which tests risky decision-making, in two independent samples of European an...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618088/ https://www.ncbi.nlm.nih.gov/pubmed/37582857 http://dx.doi.org/10.1038/s41380-023-02123-x |
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author | Nurmi, E. L. Laughlin, C. P. de Wit, H. Palmer, A. A. MacKillop, J. Cannon, T. D. Bilder, R. M. Congdon, E. Sabb, F. W. Seaman, L. C. McElroy, J. J. Libowitz, M. R. Weafer, J. Gray, J. Dean, A. C. Hellemann, G. S. London, E. D. |
author_facet | Nurmi, E. L. Laughlin, C. P. de Wit, H. Palmer, A. A. MacKillop, J. Cannon, T. D. Bilder, R. M. Congdon, E. Sabb, F. W. Seaman, L. C. McElroy, J. J. Libowitz, M. R. Weafer, J. Gray, J. Dean, A. C. Hellemann, G. S. London, E. D. |
author_sort | Nurmi, E. L. |
collection | PubMed |
description | Risky decision-making is a common, heritable endophenotype seen across many psychiatric disorders. Its underlying genetic architecture is incompletely explored. We examined behavior in the Balloon Analogue Risk Task (BART), which tests risky decision-making, in two independent samples of European ancestry. One sample (n = 1138) comprised healthy participants and some psychiatric patients (53 schizophrenia, 42 bipolar disorder, 47 ADHD); the other (n = 911) excluded for recent treatment of various psychiatric disorders but not ADHD. Participants provided DNA and performed the BART, indexed by mean adjusted pumps. We constructed a polygenic risk score (PRS) for discovery in each dataset and tested it in the other as replication. Subsequently, a genome-wide MEGA-analysis, combining both samples, tested genetic correlation with risk-taking self-report in the UK Biobank sample and psychiatric phenotypes characterized by risk-taking (ADHD, Bipolar Disorder, Alcohol Use Disorder, prior cannabis use) in the Psychiatric Genomics Consortium. The PRS for BART performance in one dataset predicted task performance in the replication sample (r = 0.13, p = 0.000012, pFDR = 0.000052), as did the reciprocal analysis (r = 0.09, p = 0.0083, pFDR=0.04). Excluding participants with psychiatric diagnoses produced similar results. The MEGA-GWAS identified a single SNP (rs12023073; p = 3.24 × 10(−8)) near IGSF21, a protein involved in inhibitory brain synapses; replication samples are needed to validate this result. A PRS for self-reported cannabis use (p = 0.00047, pFDR = 0.0053), but not self-reported risk-taking or psychiatric disorder status, predicted behavior on the BART in our MEGA-GWAS sample. The findings reveal polygenic architecture of risky decision-making as measured by the BART and highlight its overlap with cannabis use. |
format | Online Article Text |
id | pubmed-10618088 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106180882023-11-02 Polygenic contributions to performance on the Balloon Analogue Risk Task Nurmi, E. L. Laughlin, C. P. de Wit, H. Palmer, A. A. MacKillop, J. Cannon, T. D. Bilder, R. M. Congdon, E. Sabb, F. W. Seaman, L. C. McElroy, J. J. Libowitz, M. R. Weafer, J. Gray, J. Dean, A. C. Hellemann, G. S. London, E. D. Mol Psychiatry Article Risky decision-making is a common, heritable endophenotype seen across many psychiatric disorders. Its underlying genetic architecture is incompletely explored. We examined behavior in the Balloon Analogue Risk Task (BART), which tests risky decision-making, in two independent samples of European ancestry. One sample (n = 1138) comprised healthy participants and some psychiatric patients (53 schizophrenia, 42 bipolar disorder, 47 ADHD); the other (n = 911) excluded for recent treatment of various psychiatric disorders but not ADHD. Participants provided DNA and performed the BART, indexed by mean adjusted pumps. We constructed a polygenic risk score (PRS) for discovery in each dataset and tested it in the other as replication. Subsequently, a genome-wide MEGA-analysis, combining both samples, tested genetic correlation with risk-taking self-report in the UK Biobank sample and psychiatric phenotypes characterized by risk-taking (ADHD, Bipolar Disorder, Alcohol Use Disorder, prior cannabis use) in the Psychiatric Genomics Consortium. The PRS for BART performance in one dataset predicted task performance in the replication sample (r = 0.13, p = 0.000012, pFDR = 0.000052), as did the reciprocal analysis (r = 0.09, p = 0.0083, pFDR=0.04). Excluding participants with psychiatric diagnoses produced similar results. The MEGA-GWAS identified a single SNP (rs12023073; p = 3.24 × 10(−8)) near IGSF21, a protein involved in inhibitory brain synapses; replication samples are needed to validate this result. A PRS for self-reported cannabis use (p = 0.00047, pFDR = 0.0053), but not self-reported risk-taking or psychiatric disorder status, predicted behavior on the BART in our MEGA-GWAS sample. The findings reveal polygenic architecture of risky decision-making as measured by the BART and highlight its overlap with cannabis use. Nature Publishing Group UK 2023-08-15 2023 /pmc/articles/PMC10618088/ /pubmed/37582857 http://dx.doi.org/10.1038/s41380-023-02123-x Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Nurmi, E. L. Laughlin, C. P. de Wit, H. Palmer, A. A. MacKillop, J. Cannon, T. D. Bilder, R. M. Congdon, E. Sabb, F. W. Seaman, L. C. McElroy, J. J. Libowitz, M. R. Weafer, J. Gray, J. Dean, A. C. Hellemann, G. S. London, E. D. Polygenic contributions to performance on the Balloon Analogue Risk Task |
title | Polygenic contributions to performance on the Balloon Analogue Risk Task |
title_full | Polygenic contributions to performance on the Balloon Analogue Risk Task |
title_fullStr | Polygenic contributions to performance on the Balloon Analogue Risk Task |
title_full_unstemmed | Polygenic contributions to performance on the Balloon Analogue Risk Task |
title_short | Polygenic contributions to performance on the Balloon Analogue Risk Task |
title_sort | polygenic contributions to performance on the balloon analogue risk task |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618088/ https://www.ncbi.nlm.nih.gov/pubmed/37582857 http://dx.doi.org/10.1038/s41380-023-02123-x |
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