ArticleMolecules (Basel, Switzerland)2025
Precision Target Discovery for Migraine: An Integrated GWAS-eQTL-PheWAS Pipeline.
Xianting Liu, Qingming Liu, Haoning Zhu, Xiao Zhou, Xinyao Li, Ming Hu, Fu Peng, Jianguang Ji, Shu Yang
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In one paragraphArticle in Molecules (Basel, Switzerland), 2025. 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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9 authors.
Xianting LiuKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.ORCID 0009-0000-4187-0262 Qingming LiuKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Haoning ZhuKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Xiao ZhouKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Xinyao LiKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Ming HuKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.ORCID 0000-0002-3637-4130 Fu PengKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.ORCID 0000-0003-0289-4426 Jianguang JiFaculty of Health Sciences, University of Macau, Macau SAR, China.
Shu YangKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Funding
Fundamental Research Funds for the Central Universities YJ202339Sichuan University Research Funds for Basic Medicine Research and University of Macau UMDF‑TISF/2025/001/FHSSichuan University Research Funds for Graduate Education and Teaching Reform GSSCU2023120State Scholarships Foundation No. 72374151the Traditional Chinese Medicine Science and Technology Industry Innovation Team of Sichuan Province and the Multi‑ dimensional Evaluation and Product Development Innovation Team of Characteristic Traditional Chinese Medicine Resources No. 2022C001
6 · The paper itselfAbstract
Migraine is a complex neurological disorder that severely compromises quality of life. Current therapies remain inadequate, creating an urgent need for precision medicine approaches. To bridge this gap, we integrated genome-wide association studies (GWASs) and multi-tissue expression quantitative trait loci (eQTL) data. Using Mendelian randomization (SMR/HEIDI) to identify putatively causal genes, followed by colocalization analysis, protein-protein interaction networks, and gene enrichment, we prioritized druggable targets. Phenome-wide association studies (PheWASs) further assessed their potential safety profiles. We identified 31 migraine-associated genes in whole blood, 20 in brain tissue, and 9 genes shared by both whole blood and brain regions. Among 13 druggable genes identified from the DGIdb and supporting literature, 10 passed colocalization validation. Eight genes (TGFB3, CHRNB1, BACE2, THRA, NCOR2, NR1D1, CHD4, REV3L) showed interactions with known drug targets, enabling the computational prediction of 41 potential repurposable drugs. Based on target druggability, PPI (protein-protein interaction) and favorable PheWAS profiles, NR1D1, THRA, NCOR2, and CHD4 are prioritized for drug development. Additionally, MICU1, UFL1, LY6G5C, and PPP1CC emerged as novel pathophysiological factors. This study establishes a multi-omics framework for precision migraine therapy, translating genetic insights into clinically actionable targets.
Indexed as
Genome-Wide Association StudyMigraine DisordersQuantitative Trait LociDrug DiscoveryGenetic Predisposition to DiseaseHumansPhenotypePolymorphism, Single NucleotidePrecision MedicineProtein Interaction Mapsdruggable genesMendelian randomizationmigrainemolecular science
Identifiers
PMID41097341
PMCPMC12526371
What OpenQuestion holds
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LicenceCC BY
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