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Identifying the associations between genetic variants and observed traits is one of the basic problems in genomics. Existing association approaches mainly adopt the collapsing strategy for rare variants. However, these approaches largely rely on the quality of variant selection, and lose statistical power if neutral variants are collapsed together. To overcome the weaknesses, in this article, we propose a novel association approach that aims to obtain a minimal set of candidate variants. This approach incorporates an ant-colony optimization into a collapsing model. Several classes of ants are designed, and each class is assigned to one particular interval in the solution space. An ant prefers to build optimal solution on the region assigned, while it communicates with others and votes for a small number of locally optimal solutions. This framework improves the performance on searching globally optimal …