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The two-stage microbial association mapping framework massMap provides an efficient solution for microbiome-wide association analysis. By fully exploiting the microbial dependence structures of the taxonomic tree, massMap is much more powerful than the existing methods in mapping the association at the lowest available taxonomic rank such as species or genus. We applied massMap to the analyses of the American Gut Project data and other datasets and found that massMap has marked improvement than the competing methods by discovering more biologically meaningful taxa.