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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\n                    <jats:italic>Danhong<\/jats:italic>\n                    Injection (DHI), a clinically proven effective anti-SAP drug. The interrelated multitargets of DHI were divided into 32\n                    <jats:italic>On-modules<\/jats:italic>\n                    . Eleven clinical SAP phenotypes defined by the Seattle Angina Questionnaire and serum lipids were interactively associated with 14 DHI efficacy-related\n                    <jats:italic>Phe-modules.<\/jats:italic>\n                    The intrinsic polymorphic associations between SAP phenotypes and\n                    <jats:italic>Phe-modules<\/jats:italic>\n                    manifested systematic positive\/negative regulation of specific one-to-one as well as complex many-to-many relationships. These\n                    <jats:italic>Phe-modules<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1186\/s43556-026-00517-1","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T23:00:59Z","timestamp":1784329259000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modular PheWAS reveals the therapeutic heterogeneity landscape of Danghong injection on stable angina pectoris"],"prefix":"10.1186","volume":"7","author":[{"given":"Bing","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwei","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixing","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayue Darrel","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"issue":"10440","key":"517_CR1","doi-asserted-by":"publisher","first-page":"2100","DOI":"10.1016\/s0140-6736(24)00367-2","volume":"403","author":"GBD","year":"2024","unstructured":"GBD. 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