The cohort allelic sums test (CAST) is an existing grouping method in which the number of individuals with one or more mutations in a group (e.g. gene) is compared between affected and unaffected individuals [5],[26],[27]. An alternative method using a grouping approach is the Combined Multivariate and Collapsing (CMC) method [26]. In this 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]. In the CMC version used in [26], rare variants are defined as those having a minor allele frequency (MAF) of at most 1%.
