Analysis of Genetic Analysis Workshop 18 data with gene-based penalized regression.

Under the premise that multiple causal variants exist within a disease gene and that we are underpowered to detect these variants individually, a variety of methods have been developed that attempt to cluster rare variants within a gene so that the variants may gather strength from one another. These methods group variants by gene or proximity, and test one gene or marker window at a time. We propose analyzing all genes simultaneously with a penalized regression method that enables grouping of all (rare and common) variants within a gene while subgrouping rare variants, thus borrowing strength from both rare and common variants within the same gene. We apply this approach using a burden based weighting of the rare variants to the Genetic Analysis Workshop 18 data.