<p>Author Summary: Resequencing is an emerging tool for the identification of rare disease-associated mutations. Recent studies have shown that groups of multiple rare mutations together can explain a large proportion of the genetic basis for some diseases. Therefore, we propose a new statistical method for analysing a group of mutations in order to test for groupwise association with disease status. We compare the proposed weighted-sum method to alternative methods and show that it is powerful for identifying disease-associated groups of mutations, both on computer-simulated and real data. By using computer simulations, we further show that resequencing a few thousand individuals is sufficient to perform a genome-wide study of all human genes, if the proposed method is used. This study thus demonstrates that resequencing studies can identify important genetic associations, provided that specialised analysis methods, such as the proposed weighted-sum method, are used.</p>