Controlling the false discovery rate in high-dimensional linear models using model-X knockoffs and $p$-values

Abstract: In this paper, we propose novel multiple testing methods for controlling the false discovery rate (FDR) in the context of high-dimensional linear models. Our development innovatively integrates model-X knockoff techniques with debiased penalized regression estimators. The proposed approach addresses two fundamental challenges in high-dimensional statistical inference: (i) constructing valid test statistics and corresponding $p$-values in solving problems with a diverging number of model parameters, and (ii) ensuring FDR control under complex and unknown dependence structures among test statistics. A central contribution of our methodology lies in the rigorous construction and theoretical analysis of two paired sets of test statistics. Based on these test statistics, our methodology adopts two $p$-value-based multiple testing algorithms. The first applies the conventional Benjamini-Hochberg procedure, justified by the asymptotic mutual independence and normality of one set of the test statistics. The second leverages the paired structure of both sets of test statistics to improve detection power while maintaining rigorous FDR control. We provide comprehensive theoretical analysis, establishing the validity of the debiasing framework and ensuring that the proposed methods achieve proper FDR control. Extensive simulation studies demonstrate that our procedures outperform existing approaches - particularly those relying on empirical evaluations of false discovery proportions - in terms of both power and empirical control of the FDR. Notably, our methodology yields substantial improvements in settings characterized by weaker signals, smaller sample sizes, and lower pre-specified FDR levels.