Quantifying the Predictive Accuracy of a Polygenic Risk Score for Predicting Incident Cancer Cases : Application to the CARTaGENE Cohort
With the increasing use of polygenic risk scores (PRS) there is a need for adapted methods to evaluate the predictivity of these tools. In this work, we propose a new pseudo- criterion to evaluate PRS predictive accuracy for time-to-event data. This new criterion is related to the score statistic de...
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Published in | Frontiers in genetics Vol. 11; p. 408 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
24.04.2020
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Subjects | |
Online Access | Get full text |
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Summary: | With the increasing use of polygenic risk scores (PRS) there is a need for adapted methods to evaluate the predictivity of these tools. In this work, we propose a new pseudo-
criterion to evaluate PRS predictive accuracy for time-to-event data. This new criterion is related to the score statistic derived under a two-component mixture model. It evaluates the effect of the PRS on both the propensity to experience the event and on the dynamic of the event among the susceptible subjects. Simulation results show that our index has good properties. We compared our index to other implemented pseudo-
for survival data. Along with our index, two other indices have comparable good behavior when the PRS has a non-null propensity effect, and our index is the only one to detect when the PRS has only a dynamic effect. We evaluated the 5-year predictivity of an 18-single-nucleotide-polymorphism PRS for incident breast cancer cases on the CARTaGENE cohort using several pseudo-
indices. We report that our index, which summarizes both a propensity and a dynamic effect, had the highest predictive accuracy. In conclusion, our proposed pseudo-
is easy to implement and well suited to evaluate PRS for predicting incident events in cohort studies. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Paramita Saha-Chaudhuri, McGill University, Canada; Shelley B. Bull, Lunenfeld-Tananbaum Research Institute of Mount Sinai Hospital, Canada Edited by: Celia M. T. Greenwood, Lady Davis Institute (LDI), Canada This article was submitted to Statistical Genetics and Methodology, a section of the journal Frontiers in Genetics |
ISSN: | 1664-8021 1664-8021 |
DOI: | 10.3389/fgene.2020.00408 |