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Hauptverfasser: Li, Chenxi, Wu, Di, Lu, Qing
Format: Preprint
Veröffentlicht: 2024
Schlagworte:
Online-Zugang:https://arxiv.org/abs/2401.09719
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author Li, Chenxi
Wu, Di
Lu, Qing
author_facet Li, Chenxi
Wu, Di
Lu, Qing
contents Kernel-based multi-marker tests for survival outcomes use primarily the Cox model to adjust for covariates. The proportional hazards assumption made by the Cox model could be unrealistic, especially in the long-term follow-up. We develop a suite of novel multi-marker survival tests for genetic association based on the accelerated failure time model, which is a popular alternative to the Cox model due to its direct physical interpretation. The tests are based on the asymptotic distributions of their test statistics and are thus computationally efficient. The association tests can account for the heterogeneity of genetic effects across sub-populations/individuals to increase the power. All the new tests can deal with competing risks and left truncation. Moreover, we develop small-sample corrections to the tests to improve their accuracy under small samples. Extensive numerical experiments show that the new tests perform very well in various scenarios. An application to a genetic dataset of Alzheimer's disease illustrates the tests' practical utility.
format Preprint
id arxiv_https___arxiv_org_abs_2401_09719
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Kernel-based multi-marker tests of association based on the accelerated failure time model
Li, Chenxi
Wu, Di
Lu, Qing
Methodology
Kernel-based multi-marker tests for survival outcomes use primarily the Cox model to adjust for covariates. The proportional hazards assumption made by the Cox model could be unrealistic, especially in the long-term follow-up. We develop a suite of novel multi-marker survival tests for genetic association based on the accelerated failure time model, which is a popular alternative to the Cox model due to its direct physical interpretation. The tests are based on the asymptotic distributions of their test statistics and are thus computationally efficient. The association tests can account for the heterogeneity of genetic effects across sub-populations/individuals to increase the power. All the new tests can deal with competing risks and left truncation. Moreover, we develop small-sample corrections to the tests to improve their accuracy under small samples. Extensive numerical experiments show that the new tests perform very well in various scenarios. An application to a genetic dataset of Alzheimer's disease illustrates the tests' practical utility.
title Kernel-based multi-marker tests of association based on the accelerated failure time model
topic Methodology
url https://arxiv.org/abs/2401.09719