We consider two specific tests of quantitative trait association with accumulations of minor alleles across rare variants within the same functional unit. In the first of these tests, the phenotype is modelled in a linear regression framework as a function of the proportion of rare variants at which an individual carries a minor allele. In the second, the phenotype is modelled in the same regression framework, but this time as a function of the presence/absence of a minor allele at any rare variant within an individual. This collapsing approach has been previously proposed in the context of a binary trait [Li and Leal, 2008], and has been demonstrated to be powerful for detecting association with rare variants discovered through re-sequencing.
