A comparison of the likelihood ratio test and the variance-stabilising transformation-based tests for detecting association of rare variants

In a recent paper in this journal, the use of variance-stabilising transformation techniques was proposed to overcome the problem of inadequacy in normality approximation when testing association for a low-frequency variant in a case-control study. It was shown that tests based on the variance-stabilising transformations are more powerful than Fisher's exact test while controlling for type I error rate. Earlier in the journal, another study had shown that the likelihood ratio test (LRT) is superior to Fisher's exact test, Wald's test, and Pearson's X² test in testing association for low-frequency variants. Thus, it is of interest to make a direct comparison between the LRT and the tests based on the variance-stabilising transformations. In this commentary, we show that the LRT and the variance-stabilising transformation-based tests have comparable power greater than Fisher's exact test, Wald's test, and Pearson's X² test.