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Marginal screening for high-dimensional predictors of survival outcomes.

ABSTRACT: This study develops a marginal screening test to detect the presence of significant predictors for a right-censored time-to-event outcome under a high-dimensional accelerated failure time (AFT) model. Establishing a rigorous screening test in this setting is challenging, because of the right censoring and the post-selection inference. In the latter case, an implicit variable selection step needs to be included to avoid inflating the Type-I error. A prior study solved this problem by constructing an adaptive resampling test under an ordinary linear regression. To accommodate right censoring, we develop a new approach based on a maximally selected Koul-Susarla-Van Ryzin estimator from a marginal AFT working model. A regularized bootstrap method is used to calibrate the test. Our test is more powerful and less conservative than both a Bonferroni correction of the marginal tests and other competing methods. The proposed method is evaluated in simulation studies and applied to two real data sets.

SUBMITTER: Huang TJ

PROVIDER: S-EPMC6959482 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Marginal screening for high-dimensional predictors of survival outcomes.

Huang Tzu-Jung TJ McKeague Ian W IW Qian Min M

Statistica Sinica 20191001 4

This study develops a marginal screening test to detect the presence of significant predictors for a right-censored time-to-event outcome under a high-dimensional accelerated failure time (AFT) model. Establishing a rigorous screening test in this setting is challenging, because of the right censoring and the post-selection inference. In the latter case, an implicit variable selection step needs to be included to avoid inflating the Type-I error. A prior study solved this problem by constructing ...[more]

PMID: 31938013

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Project description:BackgroundThe onset of silent diseases such as type 2 diabetes is often registered through self-report in large prospective cohorts. Self-reported outcomes are cost-effective; however, they are subject to error. Diagnosis of silent events may also occur through the use of imperfect laboratory-based diagnostic tests. In this paper, we describe an approach for variable selection in high dimensional datasets for settings in which the outcome is observed with error.MethodsWe adapt the spike and slab Bayesian Variable Selection approach in the context of error-prone, self-reported outcomes. The performance of the proposed approach is studied through simulation studies. An illustrative application is included using data from the Women's Health Initiative SNP Health Association Resource, which includes extensive genotypic (>900,000 SNPs) and phenotypic data on 9,873 African American and Hispanic American women.ResultsSimulation studies show improved sensitivity of our proposed method when compared to a naive approach that ignores error in the self-reported outcomes. Application of the proposed method resulted in discovery of several single nucleotide polymorphisms (SNPs) that are associated with risk of type 2 diabetes in a dataset of 9,873 African American and Hispanic participants in the Women's Health Initiative. There was little overlap among the top ranking SNPs associated with type 2 diabetes risk between the racial groups, adding support to previous observations in the literature of disease associated genetic loci that are often not generalizable across race/ethnicity populations. The adapted Bayesian variable selection algorithm is implemented in R. The source code for the simulations are available in the Supplement.ConclusionsVariable selection accuracy is reduced when the outcome is ascertained by error-prone self-reports. For this setting, our proposed algorithm has improved variable selection performance when compared to approaches that neglect to account for the error-prone nature of self-reports.

Dataset Information

Marginal screening for high-dimensional predictors of survival outcomes.

Publications

Marginal screening for high-dimensional predictors of survival outcomes.

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