Hwang et al1 and Foppa and Spiegelman2 have presented sample size and power
calculations for gene-environment interaction in case-control studies. These calculations
have been criticized by Garcia-Closas and Lubin3 for relying on a variance estimator under
the null (the “null-variance” formula4), rather than under the alternative. The issue is not that
the null-variance sample-size calculations are incorrect, but simply that they do not
correspond to the test statistics that are generally used. In practice, the variance is most often …