Robust Association Tests for the Replication of Genome-Wide Association Studies

TL;DR

This paper shows how robust genetic tests can be used in replication studies to improve the reliability of genome-wide association study results.

Contribution

The paper introduces a method to evaluate overall statistical significance using combined p-values from discovery and replication studies.

Findings

Robust tests like MAX3 and MIN2 improve power across genetic models.

Combining p-values from discovery and replication studies enhances reliability.

The methods are effective for evaluating statistical significance in GWAS replication.

Abstract

In genome-wide association study (GWAS), robust genetic association tests such as maximum of three CATTs (MAX3), each corresponding to recessive, additive, and dominant genetic models, the minimum p value of Pearson's Chi-square test with 2 degrees of freedom, and CATT based on additive genetic model (MIN2), genetic model selection (GMS), and genetic model exclusion (GME) methods have been shown to provide better power performance under wide range of underlying genetic models. In this paper, we demonstrate how these robust tests can be applied to the replication study of GWAS and how the overall statistical significance can be evaluated using the combined test formed by p values of the discovery and replication studies.

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