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Serum Urate Polygenic Risk Score Can Improve Gout Risk Prediction: A Large-Scale Cohort Study
Gout is a painful inflammatory arthritis affecting more than 8 million Americans. Identifying high-risk patients in early life could potentially encourage people to adopt lifestyle changes to prevent gout. Polygenic risk score (PRS) provides an overall estimate of an individual's genetic liabil...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889590/ https://www.ncbi.nlm.nih.gov/pubmed/33613619 http://dx.doi.org/10.3389/fgene.2020.604219 |
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author | Zhang, Yanfei Lee, Ming Ta Michael |
author_facet | Zhang, Yanfei Lee, Ming Ta Michael |
author_sort | Zhang, Yanfei |
collection | PubMed |
description | Gout is a painful inflammatory arthritis affecting more than 8 million Americans. Identifying high-risk patients in early life could potentially encourage people to adopt lifestyle changes to prevent gout. Polygenic risk score (PRS) provides an overall estimate of an individual's genetic liability to develop a disease and can be used for early identification of high-risk individuals. In this study, we validated a previously reported PRS in an independent cohort. The urate-PRS was constructed from 110 significant urate-associated variants identified in Europeans. Phenome-wide and PRS-wide association study showed the urate-PRS is highly specifically associated with gout (phecode: 274.10; beta = 1.495 [1.372, 1.619], p = 4.37e-124). Urate-PRS alone did not performed in the gout prediction (area under the receiver operating characteristic curve, AUROC = 0.640); however, the addition of PRS upon demographics significantly improved the model performance, yielding an AUROC of 0.804 from 0.777 (DeLong test p = 3.66e−9). Trans-ethnic PRS and European-specific PRS showed similar prediction performance. We observed increasing gout prevalence and odds ratio (OR) across the PRS quintiles. Our study showed 8.2% of the cohort had more than 2.5 odds for gout than remainders, indicating that urate-PRS may be a better marker than age and sex to stratify patient risk. With the rapid growth of large biorepositories, such as All of Us, urate-PRS can be applied quickly and widely in population to estimate individual's risk, providing a powerful tool for gout preventive purpose in population health. |
format | Online Article Text |
id | pubmed-7889590 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78895902021-02-19 Serum Urate Polygenic Risk Score Can Improve Gout Risk Prediction: A Large-Scale Cohort Study Zhang, Yanfei Lee, Ming Ta Michael Front Genet Genetics Gout is a painful inflammatory arthritis affecting more than 8 million Americans. Identifying high-risk patients in early life could potentially encourage people to adopt lifestyle changes to prevent gout. Polygenic risk score (PRS) provides an overall estimate of an individual's genetic liability to develop a disease and can be used for early identification of high-risk individuals. In this study, we validated a previously reported PRS in an independent cohort. The urate-PRS was constructed from 110 significant urate-associated variants identified in Europeans. Phenome-wide and PRS-wide association study showed the urate-PRS is highly specifically associated with gout (phecode: 274.10; beta = 1.495 [1.372, 1.619], p = 4.37e-124). Urate-PRS alone did not performed in the gout prediction (area under the receiver operating characteristic curve, AUROC = 0.640); however, the addition of PRS upon demographics significantly improved the model performance, yielding an AUROC of 0.804 from 0.777 (DeLong test p = 3.66e−9). Trans-ethnic PRS and European-specific PRS showed similar prediction performance. We observed increasing gout prevalence and odds ratio (OR) across the PRS quintiles. Our study showed 8.2% of the cohort had more than 2.5 odds for gout than remainders, indicating that urate-PRS may be a better marker than age and sex to stratify patient risk. With the rapid growth of large biorepositories, such as All of Us, urate-PRS can be applied quickly and widely in population to estimate individual's risk, providing a powerful tool for gout preventive purpose in population health. Frontiers Media S.A. 2021-02-04 /pmc/articles/PMC7889590/ /pubmed/33613619 http://dx.doi.org/10.3389/fgene.2020.604219 Text en Copyright © 2021 Zhang and Lee. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Zhang, Yanfei Lee, Ming Ta Michael Serum Urate Polygenic Risk Score Can Improve Gout Risk Prediction: A Large-Scale Cohort Study |
title | Serum Urate Polygenic Risk Score Can Improve Gout Risk Prediction: A Large-Scale Cohort Study |
title_full | Serum Urate Polygenic Risk Score Can Improve Gout Risk Prediction: A Large-Scale Cohort Study |
title_fullStr | Serum Urate Polygenic Risk Score Can Improve Gout Risk Prediction: A Large-Scale Cohort Study |
title_full_unstemmed | Serum Urate Polygenic Risk Score Can Improve Gout Risk Prediction: A Large-Scale Cohort Study |
title_short | Serum Urate Polygenic Risk Score Can Improve Gout Risk Prediction: A Large-Scale Cohort Study |
title_sort | serum urate polygenic risk score can improve gout risk prediction: a large-scale cohort study |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889590/ https://www.ncbi.nlm.nih.gov/pubmed/33613619 http://dx.doi.org/10.3389/fgene.2020.604219 |
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