Joint effect of multiple common SNPs predicts melanoma susceptibility

Shenying Fang, Jiali Han, Mingfeng Zhang, Li E. Wang, Qingyi Wei, Christopher I. Amos, Jeffrey E. Lee

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere85642
JournalPloS one
Volume8
Issue number12
DOIs
StatePublished - Dec 31 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Fang, S., Han, J., Zhang, M., Wang, L. E., Wei, Q., Amos, C. I., & Lee, J. E. (2013). Joint effect of multiple common SNPs predicts melanoma susceptibility. PloS one, 8(12), [e85642]. https://doi.org/10.1371/journal.pone.0085642