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Predictive accuracy of combined genetic and environmental risk scores.

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journal contribution
posted on 2018-01-09, 11:58 authored by Frank Dudbridge, Nora Pashayan, Jian Yang
The substantial heritability of most complex diseases suggests that genetic data could provide useful risk prediction. To date the performance of genetic risk scores has fallen short of the potential implied by heritability, but this can be explained by insufficient sample sizes for estimating highly polygenic models. When risk predictors already exist based on environment or lifestyle, two key questions are to what extent can they be improved by adding genetic information, and what is the ultimate potential of combined genetic and environmental risk scores? Here, we extend previous work on the predictive accuracy of polygenic scores to allow for an environmental score that may be correlated with the polygenic score, for example when the environmental factors mediate the genetic risk. We derive common measures of predictive accuracy and improvement as functions of the training sample size, chip heritabilities of disease and environmental score, and genetic correlation between disease and environmental risk factors. We consider simple addition of the two scores and a weighted sum that accounts for their correlation. Using examples from studies of cardiovascular disease and breast cancer, we show that improvements in discrimination are generally small but reasonable degrees of reclassification could be obtained with current sample sizes. Correlation between genetic and environmental scores has only minor effects on numerical results in realistic scenarios. In the longer term, as the accuracy of polygenic scores improves they will come to dominate the predictive accuracy compared to environmental scores.

Funding

This work is supported by the MRC (MR/K006215/1, MR/M026175/1).

History

Citation

Genetic Epidemiology, 2017, 1–16.

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Health Sciences

Version

  • VoR (Version of Record)

Published in

Genetic Epidemiology

Publisher

Wiley for International Genetic Epidemiology Society (IGES)

issn

0741-0395

eissn

1098-2272

Acceptance date

2017-09-27

Copyright date

2017

Available date

2018-01-09

Publisher version

http://onlinelibrary.wiley.com/doi/10.1002/gepi.22092/full

Notes

Additional Supporting Information may be found online in the supporting information tab for this article.

Language

en

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