Traditional image genetics primarily uses linear models to investigate the relationship between brain image data and genetic data for Alzheimer’s disease (AD) and does not take into account the dynamic changes in brain phenotype and connectivity data across time between different brain areas. In this work, we proposed a novel method that combined Deep Subspace reconstruction with Hypergraph-Based Temporally-constrained Group Sparse Canonical Correlation Analysis (DS-HBTGSCCA) to discover the deep association between longitudinal phenotypes and genotypes. The proposed method made full use of dynamic high-order correlation between brain regions. In this method, the deep subspace reconstruction technique was applied to retrieve the nonlinear properties of the original data, and hypergraphs were used to mine the high-order correlation between two types of rebuilt data. The molecular biological analysis of the experimental findings demonstrated that our algorithm was capable of extracting more valuable time series correlation from the real data obtained by the AD neuroimaging program and finding AD biomarkers across multiple time points. Additionally, we used regression analysis to verify the close relationship between the extracted top brain areas and top genes and found the deep subspace reconstruction approach with a multi-layer neural network was helpful in enhancing clustering performance.