Abstract
There are four tests - the likelihood ratio (LR) test, Wald's test, the score test and the exact test - commonly employed in genetic association studies. On comparison of the four tests, we found that Wald's test, popular in genome-wide screens due to its low computational demands, exhibited a paradoxical behaviour in that the test statistic decreased as the effect size of the variant increased, resulting in a loss of power. The LR test always achieved the most significant P-values, followed by the exact test. We further examined the results in a real data set composed of high- and low-cholesterol subjects from the Dallas Heart Study (DHS). We also compared the single-variant LR test with two multi-variant analysis approaches - the burden test and the C-alpha test - in analysing the sequencing data by simulation. Our results call for caution in using Wald's test in genome-wide case-control association studies and suggest that the LR test is a better alternative in spite of its computational demands.
Original language | English (US) |
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Pages (from-to) | 168-177 |
Number of pages | 10 |
Journal | Annals of Human Genetics |
Volume | 76 |
Issue number | 2 |
DOIs | |
State | Published - Mar 2012 |
Keywords
- Case-control study
- Low-frequency variants
- Wald's test
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)