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Joint Effect of Multiple Common SNPs Predicts Melanoma Susceptibility
Single genetic variants discovered so far have been only weakly associated with melanoma. This study aims to use multiple single nucleotide polymorphisms (SNPs) jointly to obtain a larger genetic effect and to improve the predictive value of a conventional phenotypic model. We analyzed 11 SNPs that...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877376/ https://www.ncbi.nlm.nih.gov/pubmed/24392023 http://dx.doi.org/10.1371/journal.pone.0085642 |
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author | Fang, Shenying Han, Jiali Zhang, Mingfeng Wang, Li-e Wei, Qingyi Amos, Christopher I. Lee, Jeffrey E. |
author_facet | Fang, Shenying Han, Jiali Zhang, Mingfeng Wang, Li-e Wei, Qingyi Amos, Christopher I. Lee, Jeffrey E. |
author_sort | Fang, Shenying |
collection | PubMed |
description | Single genetic variants discovered so far have been only weakly associated with melanoma. This study aims to use multiple single nucleotide polymorphisms (SNPs) jointly to obtain a larger genetic effect and to improve the predictive value of a conventional phenotypic model. We analyzed 11 SNPs that were associated with melanoma risk in previous studies and were genotyped in MD Anderson Cancer Center (MDACC) and Harvard Medical School investigations. Participants with ≥15 risk alleles were 5-fold more likely to have melanoma compared to those carrying ≤6. Compared to a model using the most significant single variant rs12913832, the increase in predictive value for the model using a polygenic risk score (PRS) comprised of 11 SNPs was 0.07(95% CI, 0.05-0.07). The overall predictive value of the PRS together with conventional phenotypic factors in the MDACC population was 0.69 (95% CI, 0.64-0.69). PRS significantly improved the risk prediction and reclassification in melanoma as compared with the conventional model. Our study suggests that a polygenic profile can improve the predictive value of an individual gene polymorphism and may be able to significantly improve the predictive value beyond conventional phenotypic melanoma risk factors. |
format | Online Article Text |
id | pubmed-3877376 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38773762014-01-03 Joint Effect of Multiple Common SNPs Predicts Melanoma Susceptibility Fang, Shenying Han, Jiali Zhang, Mingfeng Wang, Li-e Wei, Qingyi Amos, Christopher I. Lee, Jeffrey E. PLoS One Research Article Single genetic variants discovered so far have been only weakly associated with melanoma. This study aims to use multiple single nucleotide polymorphisms (SNPs) jointly to obtain a larger genetic effect and to improve the predictive value of a conventional phenotypic model. We analyzed 11 SNPs that were associated with melanoma risk in previous studies and were genotyped in MD Anderson Cancer Center (MDACC) and Harvard Medical School investigations. Participants with ≥15 risk alleles were 5-fold more likely to have melanoma compared to those carrying ≤6. Compared to a model using the most significant single variant rs12913832, the increase in predictive value for the model using a polygenic risk score (PRS) comprised of 11 SNPs was 0.07(95% CI, 0.05-0.07). The overall predictive value of the PRS together with conventional phenotypic factors in the MDACC population was 0.69 (95% CI, 0.64-0.69). PRS significantly improved the risk prediction and reclassification in melanoma as compared with the conventional model. Our study suggests that a polygenic profile can improve the predictive value of an individual gene polymorphism and may be able to significantly improve the predictive value beyond conventional phenotypic melanoma risk factors. Public Library of Science 2013-12-31 /pmc/articles/PMC3877376/ /pubmed/24392023 http://dx.doi.org/10.1371/journal.pone.0085642 Text en © 2013 Fang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Fang, Shenying Han, Jiali Zhang, Mingfeng Wang, Li-e Wei, Qingyi Amos, Christopher I. Lee, Jeffrey E. Joint Effect of Multiple Common SNPs Predicts Melanoma Susceptibility |
title | Joint Effect of Multiple Common SNPs Predicts Melanoma Susceptibility |
title_full | Joint Effect of Multiple Common SNPs Predicts Melanoma Susceptibility |
title_fullStr | Joint Effect of Multiple Common SNPs Predicts Melanoma Susceptibility |
title_full_unstemmed | Joint Effect of Multiple Common SNPs Predicts Melanoma Susceptibility |
title_short | Joint Effect of Multiple Common SNPs Predicts Melanoma Susceptibility |
title_sort | joint effect of multiple common snps predicts melanoma susceptibility |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877376/ https://www.ncbi.nlm.nih.gov/pubmed/24392023 http://dx.doi.org/10.1371/journal.pone.0085642 |
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