Gene-level pharmacogenetic analysis on survival outcomes using gene-trait similarity regression

DOI10.1214/14-AOAS735zbMATH Open1454.62412arXiv1408.0083OpenAlexW3105010080WikidataQ33881221 ScholiaQ33881221MaRDI QIDQ400685FDOQ400685

Authors: Jung-Ying Tzeng, Wenbin Lu, Fang-Chi Hsu 

Publication date: 22 August 2014

Published in: The Annals of Applied Statistics (Search for Journal in Brave)

Abstract: Gene/pathway-based methods are drawing significant attention due to their usefulness in detecting rare and common variants that affect disease susceptibility. The biological mechanism of drug responses indicates that a gene-based analysis has even greater potential in pharmacogenetics. Motivated by a study from the Vitamin Intervention for Stroke Prevention (VISP) trial, we develop a gene-trait similarity regression for survival analysis to assess the effect of a gene or pathway on time-to-event outcomes. The similarity regression has a general framework that covers a range of survival models, such as the proportional hazards model and the proportional odds model. The inference procedure developed under the proportional hazards model is robust against model misspecification. We derive the equivalence between the similarity survival regression and a random effects model, which further unifies the current variance component-based methods. We demonstrate the effectiveness of the proposed method through simulation studies. In addition, we apply the method to the VISP trial data to identify the genes that exhibit an association with the risk of a recurrent stroke. The TCN2 gene was found to be associated with the recurrent stroke risk in the low-dose arm. This gene may impact recurrent stroke risk in response to cofactor therapy.

Full work available at URL: https://arxiv.org/abs/1408.0083

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zbMATH Keywords

proportional hazards modelproportional odds modelsurvival dataassociation studygene/pathwaypharmacogeneticssimilarity regression

Mathematics Subject Classification ID

Estimation in survival analysis and censored data (62N02) Applications of statistics to biology and medical sciences; meta analysis (62P10)

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Cited In (1)

• A penalized likelihood approach for investigating gene-drug interactions in pharmacogenetic studies

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