A Robust Approach for Identifying Gene-Environment Interactions for Prognosis

TL;DR

This paper introduces a robust statistical method for identifying gene-environment interactions affecting prognosis, effectively handling data contamination and outperforming existing methods in simulations and real cancer data analysis.

Contribution

It proposes a novel robust AFT model with exponential squared loss and regularization, improving gene-environment interaction detection under contaminated data conditions.

Findings

Outperforms unrobust methods in contaminated data scenarios.

Identifies novel gene-environment interactions in lung cancer data.

Demonstrates stability and clinical relevance of identified markers.

Abstract

For many complex diseases, prognosis is of essential importance. It has been shown that, beyond the main effects of genetic (G) and environmental (E) risk factors, the gene-environment (G$\times$E) interactions also play a critical role. In practice, the prognosis outcome data can be contaminated, and most of the existing methods are not robust to data contamination. In the literature, it has been shown that even a single contaminated observation can lead to severely biased model estimation. In this study, we describe prognosis using an accelerated failure time (AFT) model. An exponential squared loss is proposed to accommodate possible data contamination. A penalization approach is adopted for regularized estimation and marker selection. The proposed method is realized using an effective coordinate descent (CD) and minorization maximization (MM) algorithm. Simulation shows that without contamination, the proposed method has performance comparable to or better than the unrobust alternative. With contamination, it outperforms the unrobust alternative and, under certain scenarios, can be superior to the robust method based on quantile regression. The proposed method is applied to the analysis of TCGA (The Cancer Genome Atlas) lung cancer data. It identifies interactions different from those using the alternatives. The identified marker have important implications and satisfactory stability.