Brain imaging genetics aims to explore the association between genetic factors such as single nucleotide polymorphisms (SNPs) and brain imaging quantitative traits (QTs). However, most existing methods do not consider the nonlinear correlations between genotypic and phenotypic data, as well as potential higher-order relationships among subjects when identifying bi-multivariate associations. In this paper, a novel method called deep hyper-Laplacian regularized self-representation learning based structured association analysis (DHRSAA) is proposed which can learn genotype-phenotype associations and obtain relevant biomarkers. Specifically, a deep neural network is used first to explore the nonlinear relationships among samples. Secondly, self-representation learning based on hyper-Laplacian regularization is utilized to reconstruct the original data. In particular, the introduction of hyper-Laplacian regularization ensures the local structure of the high-dimensional spatial embedding and explores the higher-order relationships among the samples. Moreover, the structural regularization term in the association analysis uncovers chain relationships among SNPs and graphical relationships among imaging QTs, thus making the obtained markers more interpretable and enhancing the biological significance of the method. The performance of the proposed method is validated on real neuroimaging genetics data. Experimental results show that DHRSAA displays better canonical correlation coefficients and recognizes clearer canonical weight patterns compared to several state-of-the-art methods, which suggests that the proposed DHRSAA achieves better performance and identifies disease-related biomarkers.

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http://dx.doi.org/10.1016/j.ymeth.2025.01.017DOI Listing

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