Differential analysis of gene-level expression is a commonly used approach for identifying disease-associated genes. Recently, intron retention (IR) has been shown to be associated with complex diseases such as cancers. IR provides value that is complementary to traditional gene-level expression. However, a systematic method to exploit IR for identifying disease-associated genes remains largely unexplored. We developed a pipeline to identify the disease-associated gene based on differential intron retention (IRDAG), which integrates IR events detected by two methods, IRFinder and iREAD. We applied it to Alzheimer’s disease (AD). We found that many of the differential genes detected based on IR were not able to be discovered by the traditional gene-level differential expression method, suggesting that our method is complementary to traditional methods. We showed that the differential genes identified with IRDAG were functionally related to AD based on the analysis of protein-protein interaction networks and brain-specific functional gene networks. Being complementary to the existing method, IRDAG provides a new and generic approach for identifying the disease-associated gene.