Rank-Based Robust Tests for Quantitative-Trait Genetic Association Studies

Standard linear regression is commonly used for genetic association studies of quantitative traits. This approach may not be appropriate if the trait, on its original or transformed scales, does not follow a normal distribution. A rank-based nonparametric approach that does not rely on any distributional assumptions can be an attractive alternative. Although several nonparametric tests exist in the literature, their performance in the genetic association setting is not well studied. We evaluate various nonparametric tests for the analysis of quantitative traits and propose a new class of nonparametric tests that have robust performance for traits with various distributions and under different genetic models. We demonstrate the advantage of our proposed methods through simulation study and real data applications.