ArticleMolecular biomedicine2026
Modular PheWAS reveals the therapeutic heterogeneity landscape of Danghong injection on stable angina pectoris.
Article in Molecular biomedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Stable angina pectoris (SAP) is a common risk factor for myocardial infarction and death. The genomic, transcriptomic, and phenomic heterogeneities of SAP require combination therapies. Multi-target drugs with fixed doses are emerging as scalable and promising prevention and therapeutic strategies for SAP. However, the identification of targets and underlying mechanisms of multi-target drugs for optimal clinical efficacy remains insurmountable. Here, we report a modular phenome-wide association study (MoPheWAS) of Danhong Injection (DHI), a clinically proven effective anti-SAP drug. The interrelated multitargets of DHI were divided into 32 On-modules. Eleven clinical SAP phenotypes defined by the Seattle Angina Questionnaire and serum lipids were interactively associated with 14 DHI efficacy-related Phe-modules. The intrinsic polymorphic associations between SAP phenotypes and Phe-modules manifested systematic positive/negative regulation of specific one-to-one as well as complex many-to-many relationships. These Phe-modules were conserved, transformed, or newly emerged modules involving G-protein-coupled receptor signaling and kinase binding. In vitro RNAi analysis confirmed the hub genes GALR1/BCMO1 in Mod-29 as multiple targets for the anti-ischemic effect of DHI. The landscape of modular regulators and polymorphic phenomic associations revealed the multi-target mechanisms underlying the therapeutic heterogeneity of SAP. Therefore, MoPheWAS may provides a novel systematic paradigm for identifying multiple phenomic targets of complex polygenic diseases.
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