In this article, the authors propose a statistical method by Testing an Optimally Weighted Combination of Multiple traits (TOW-CM) to test the association between multiple traits and multiple variants in a genomic region (a gene or pathway). They investigate the performance of the proposed method through extensive simulation studies. Their simulation studies show that the proposed method has correct type I error rates and is either the most powerful test or comparable with the most powerful tests. Additionally, they illustrate the usefulness of TOW-CM based on a COPDGene study.