Abstract
Testing for the Hardy-Weinberg equilibrium (HWE) is often used as an initial step for checking the quality of genotyping. When testing the HWE for case-control data, the impact of a potential genetic association between the marker and the disease must be controlled for otherwise the results may be biased. Li and Li [2008] proposed a likelihood ratio test (LRT) that accounts for this potential genetic association and it is more powerful than the commonly used control-only χ2 test. However, the LRT is not efficient when the marker is independent of the disease, and also requires numerical optimization to calculate the test statistic. In this article, we propose a novel shrinkage test for assessing the HWE. The proposed shrinkage test yields higher statistical power than the LRT when the marker is independent of or weakly associated with the disease, and converges to the LRT when the marker is strongly associated with the disease. In addition, the proposed shrinkage test has a closed form and can be easily used to test the HWE for large datasets that result from genome-wide association studies. We compare the performance of the shrinkage test with existing methods using simulation studies, and apply the shrinkage test to a genome-wide association dataset for Alzheimer's disease.
Original language | English (US) |
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Pages (from-to) | 743-750 |
Number of pages | 8 |
Journal | Genetic epidemiology |
Volume | 37 |
Issue number | 7 |
DOIs | |
State | Published - Nov 2013 |
Keywords
- Bayesian factor
- Case-control study
- Hardy-Weinberg equilibrium
- Shrinkage test
ASJC Scopus subject areas
- Epidemiology
- Genetics(clinical)
MD Anderson CCSG core facilities
- Biostatistics Resource Group