IntroductionBrain imaging genetics aims to explore the genetic architecture underlying brain structure and functions. Recent studies showed that the incorporation of prior knowledge, such as subject diagnosis information and brain regional correlation, can help identify significantly stronger imaging genetic associations. However, sometimes such information may be incomplete or even unavailable.MethodsIn this study, we explore a new data-driven prior knowledge that captures the subject-level similarity by fusing multi-modal similarity networks. It was incorporated into the sparse canonical correlation analysis (SCCA) model, which is aimed to identify a small set of brain imaging and genetic markers that explain the similarity matrix supported by both modalities. It was applied to amyloid and tau imaging data of the ADNI cohort, respectively.ResultsFused similarity matrix across imaging and genetic data was found to improve the association performance better or similarly well as diagnosis information, and therefore would be a potential substitute prior when the diagnosis information is not available (i.e., studies focused on healthy controls).DiscussionOur result confirmed the value of all types of prior knowledge in improving association identification. In addition, the fused network representing the subject relationship supported by multi-modal data showed consistently the best or equally best performance compared to the diagnosis network and the co-expression network.