The CMC method is implemented according to the description in [26]. In brief, for the CMC method all rare variants are collapsed, as in the CAST method, and the collapsed variants are treated as a single common variant which is analysed together with the other common variants using multivariate analysis [26]. We used the Fisher product method [42],[43] for multivariate analysis, rather than the Hotelling's T 2 method, because it allows for one-sided testing, and hence allowed a fair comparison for the CMC method. Note that if a two-sided test were used for the CMC method, the power estimates would then have been too low compared to the variant-by-variant and weighted-sum methods.
