A Generalized Kruskal–Wallis Test Incorporating Group Uncertainty with Application to Genetic Association Studies

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Abstract

Summary

Motivated by genetic association studies of SNPs with genotype uncertainty, we propose a generalization of the Kruskal–Wallis test that incorporates group uncertainty when comparing k samples. The extended test statistic is based on probability-weighted rank-sums and follows an asymptotic chi-square distribution with k − 1 degrees of freedom under the null hypothesis. Simulation studies confirm the validity and robustness of the proposed test in finite samples. Application to a genome-wide association study of type 1 diabetic complications further demonstrates the utilities of this generalized Kruskal–Wallis test for studies with group uncertainty. The method has been implemented as an open-resource R program, GKW.

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