ArticleThe journal of headache and pain2024
Multi-omics Mendelian randomization integrating GWAS, eQTL and pQTL data revealed GSTM4 as a potential drug target for migraine.
Article in The journal of headache and pain, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 2 of them syntheses that pooled it.
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66 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Genome-Wide Meta-Analysis of Parkinson's Disease Associated Genetic Loci and Validation of Therapeutic Targets.Brain and behavior · 2025Pooled it
- Integrative Approaches Identify Genetic Determinants of Levodopa Induced Dyskinesia.Molecular neurobiology · 2025Pooled it
- Integrative multi-omics Mendelian randomization reveals key lipid metabolism genes as therapeutic targets for diabetic nephropathy pathogenesis.Renal failure · 2026Article
- Identification of key molecules and pathways in CaOx crystal-induced renal injury based on metabolomics and proteomics.International urology and nephrology · 2026Article
- Integrative Proteogenomics and Single-Cell Transcriptomics Prioritize Candidate Causal Proteins and Therapeutic Targets in Age-Related Macular Degeneration.International journal of molecular sciences · 2026Article
- Integrating multi-omics and mendelian randomization identifies therapeutic targets for Lichen Sclerosus: A druggable genome-wide study.Global medical genetics · 2026Article
- Advancing PCOS drug development: multi-omics discovery of key targets and repurposable compounds.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Causal Relationship Between Vitamin D and Anxiety and Depression: A Bidirectional Mendelian Randomization Study.Actas espanolas de psiquiatria · 2026Article
- Multi-omics and artificial intelligence for precision drug discovery and potential clinical applications.Signal transduction and targeted therapy · 2026Review
- Integrative multi-omics analysis identifies key ubiquitination regulators in prostate cancer.Translational oncology · 2026Article
- Proteome-wide genetic study identified therapeutic targets for early-onset and late-onset Alzheimer's disease.International journal of surgery (London, England) · 2026Article
- Article
- Decoding causal m6A: a bioinformatics roadmap for psychiatric disorders.Briefings in bioinformatics · 2026Review
- Moving Mendelian Randomization From Traditional Risk Factors to Molecular Targets for Drug Development and Clinical Trials in Nephrology.Kidney international reports · 2026Review
- Integrating single-cell transcriptomics and epigenetics in a multi-omics MR framework identifies PARK7 as a causal gene in streptococcal septicemia.Epigenetics & chromatin · 2026Article
- Beyond the baseline: mapping the context-specific regulatory landscape of disease.Trends in genetics : TIG · 2026Review
- Integrative analysis via bioinformatics and machine learning identifies SERPING1 as a biomarker candidate for major depressive disorder.BMC psychiatry · 2026Article
- Unraveling the Cross-Tissue Neuroimmune-Vascular Genetic Architecture of Migraine Using Integrated Multi-Omics, Single-Cell, and Spatial Transcriptomics: Prioritizing T-Cell Regulatory Networks and Peripheral Targets.International journal of molecular sciences · 2026Article
- Systematic druggable genome-wide Mendelian randomization identifies therapeutic targets for gout.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Natural Selection-Guided ACE2-Targeted Molecular Imaging: A New Paradigm for PET Tracer Development.Chemical & biomedical imaging · 2026Article
6 more citing papers are in PubMed but not listed here.
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10 authors.
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Abstract
introductionMigraine, as a complex neurological disease, brings heavy burden to patients and society. Despite the availability of established therapies, existing medications have limited efficacy. Thus, we aimed to find the drug targets that improve the prognosis of migraine.
methodWe used Mendelian Randomization (MR) and Summary-data-based MR (SMR) analyses to study possible drug targets of migraine by summary statistics from FinnGen cohorts (nCase = 44,616, nControl = 367,565), with further replication in UK Biobank (nCase = 26,052, nControl = 487,214). Genetic instruments were obtained from eQTLGen and UKB-PPP to verify the drug targets at the gene expression and protein levels. The additional analyses including Bayesian co-localization, the heterogeneity in dependent instruments(HEIDI), Linkage Disequilibrium Score(LDSC), bidirectional MR, multivariate MR(MVMR), heterogeneity test, horizontal pleiotropy test, and Steiger filtering were implemented to consolidate the findings further. Lastly, drug prediction analysis and phenome-wide association study(PheWAS) were employed to imply the possibility of drug targets for future clinical applications.
resultThe MR analysis of eQTL data showed that four drug targets (PROCR, GSTM4, SLC4A1, and TNFRSF10A) were significantly associated with migraine risk in both the FinnGen and UK Biobank cohorts. However, only GSTM4 exhibited consistent effect directions across the two outcomes(Discovery cohort: OR(95%CI) = 0.94(0.93-0.96); p = 2.70e - 10; Replication cohort: OR(95%CI) = 0.93(0.91-0.94); p = 4.21e - 17). Furthermore, GSTM4 passed the SMR at p < 0.05 and HEIDI test at p > 0.05 at both the gene expression and protein levels. The protein-level MR analysis revealed a strong correlation between genetically predicted GSTM4 with a lower incidence of migraine and its subtypes(Overall migraine: OR(95%CI) = 0.91(0.87-0.95); p = 6.98e-05; Migraine with aura(MA): OR(95%CI) = 0.90(0.85-0.96); p = 2.54e-03; Migraine without aura(MO): OR(95%CI) = 0.90(0.83-0.96); p = 2.87e-03), indicating a strong co-localization relationship (PPH4 = 0.86). Further analyses provided additional validation for the possibility of GSTM4 as a migraine treatment target.
conclusionThis study identifies GSTM4 as a potential druggable gene and promising therapeutic target for migraine.
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