Bayes Factor Based on the Trend Test Incorporating Hardy–Weinberg Disequilibrium: More Power to Detect Genetic Association

Abstract

In the analysis of case-control genetic association, the trend test and Pearson's test are the two most commonly used tests. In genome-wide association studies (GWAS), Bayes factor (BF) is a useful tool to support significant P-values, and a better measure than P-value when results are compared across studies with different sample sizes. When reporting the P-value of the trend test, we propose a BF directly based on the trend test. To improve the power to detect association under recessive or dominant genetic models, we propose a BF based on the trend test and incorporating Hardy-Weinberg disequilibrium in cases. When the true model is unknown, or both the trend test and Pearson's test or other robust tests are applied in genome-wide scans, we propose a joint BF, combining the previous two BFs. All three BFs studied in this paper have closed forms and are easy to compute without integrations, so they can be reported along with P-values, especially in GWAS. We discuss how to use each of them and how to specify priors. Simulation studies and applications to three GWAS are provided to illustrate their usefulness to detect nonadditive gene susceptibility in practice.