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Statistics in Medicine
Article . 2019 . Peer-reviewed
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Article . 2019
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https://dx.doi.org/10.48550/ar...
Article . 2018
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A general approach to detect gene (G)‐environment (E) additive interaction leveraging G‐E independence in case‐control studies

A general approach to detect gene (G)-environment (E) additive interaction leveraging G-E independence in case-control studies
Authors: Eric J. Tchetgen Tchetgen; Xu Shi; Benedict H.W. Wong; Tamar Sofer;

A general approach to detect gene (G)‐environment (E) additive interaction leveraging G‐E independence in case‐control studies

Abstract

It is increasingly of interest in statistical genetics to test for the presence of an additive interaction between genetic (G) and environmental (E) risk factors. In case‐control studies involving a rare disease, a statistical test of no additive G×E interaction typically entails a test of no relative excess risk due to interaction (RERI). It has been shown that a likelihood ratio test of a null RERI incorporating the G‐E independence assumption (RERI‐LRT) outperforms the standard approach. The RERI‐LRT relies on correct specification of a logistic model for the binary outcome, as a function of G, E, and auxiliary covariates. However, when at least one exposure is not categorical or auxiliary covariates are present, nonparametric estimation may not be feasible, while parametric logistic regression will a priori rule out the null hypothesis of no additive interaction in most practical situations, inflating type I error rate. In this paper, we present a general approach to test for G × E additive interaction exploiting G‐E independence. Unlike the RERI‐LRT, it allows the regression model for the binary outcome to remain unrestricted, and nonetheless still allows for covariate adjustment in order to ensure the G‐E independence assumption or to rule out residual confounding. The methods are illustrated through extensive simulation studies and an ovarian cancer study.

Keywords

gene-environment independence, Ovarian Neoplasms, FOS: Computer and information sciences, Models, Statistical, case-control study, gene-environment additive interaction, Applications of statistics to biology and medical sciences; meta analysis, Methodology (stat.ME), Risk Factors, Case-Control Studies, Humans, Computer Simulation, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Statistics - Methodology

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
3
Average
Average
Average
Green
bronze
Related to Research communities
Cancer Research