Identifying important gene signatures of BMI using network structure-aided nonparametric quantile regression.

Abstract

We focus on identifying genomics risk factors of higher body mass index (BMI) incorporating a priori information, such as biological pathways. However, the commonly used methods to incorporate prior information provide a model for the mean function of the outcome and rely on unmet assumptions. To address these concerns, we propose a method for nonparametric additive quantile regression with network regularization to incorporate the information encoded by known networks. To account for nonlinear associations, we approximate the unknown additive functional effect of each predictor with the expansion of a B-spline basis. We implement the group Lasso penalty to obtain a sparse model. We define the network-constrained penalty by the total norm of the difference between the effect functions of any two linked genes in the known network. We further propose an efficient computation procedure to solve the optimization problem that arises in our model. Simulation studies show that our proposed method performs well in identifying more truly associated genes and less falsely associated genes than alternative approaches. We apply the proposed method to analyze the microarray gene-expression dataset in the Framingham Heart Study and identify several 75 percentile BMI associated genes. In conclusion, our proposed approach efficiently identifies the outcome-associated variables in a nonparametric additive quantile regression framework by leveraging known network information.