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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...

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Autores principales: Zhang, Yanfei, Lee, Ming Ta Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
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.
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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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