Abstract: A novel set of methods for gene-based tests of association are provided. By gathering multiple independent effects into a single test, GWiS has greater power than conventional tests to identify genes with multiple causal variants. GWiS also retains power for low-frequency minor alleles that are increasingly important for personal genetics, a feature not shared by other multi-SNP tests. The methods of the present invention can be combined with conventional computing platforms to provide a new analytical tool for analyzing genes which are linked to multiple traits.