Most studies assessing associations between rare variants and a phenotype have relied on rather simple collapsing strategies (Table 1). The advantages of more sophisticated data analysis methods are therefore unclear from a practical and implementation standpoint. However, power studies comparing newer methods with more simplistic methods for rare variant analysis have been pursued (Table 3). The studies we list in Table 3 are in no way exhaustive, but their consideration can provide insight into the limitations of the different strategies and, therefore, motivation for further studies. For example, almost all such studies consider comparisons between a proposed novel method and simple single locus analyses, which is an obvious comparison at some level, but does not reflect the sophistication and utility of the proposed method. In addition, almost all of the studies considered simulations under some version of the EAH model of rare variant effects and do not consider other scenarios (Figure 2) or the influence of LD structure among multiple common and rare variants (of the type that might create ‘synthetic associations’85). In addition, studies so far have not considered
