Genome-wide association study-driven identification of thrombomodulin and factor V as the best biomarker combination for deep vein thrombosis
Abstract Deep vein thrombosis (DVT) is a clinically significant condition characterized by the formation of thrombi in deep venous structures, leading to high morbidity and potential mortality. Identifying reliable biomarkers for DVT risk prediction remains challenging due to the intricate genetic a...
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BioMed Central
2025-05-01
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| Series: | Genomics & Informatics |
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| Online Access: | https://doi.org/10.1186/s44342-025-00047-2 |
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| author | Usi Sukorini Gisca Ajeng Widya Ninggar Mohammad Hendra Setia Lesmana Lalu Irham Wirawan Adikusuma Hegaria Rahmawati Nur Imma Fatimah Harahap Chiou-Feng Lin Rahmat Dani Satria |
| author_facet | Usi Sukorini Gisca Ajeng Widya Ninggar Mohammad Hendra Setia Lesmana Lalu Irham Wirawan Adikusuma Hegaria Rahmawati Nur Imma Fatimah Harahap Chiou-Feng Lin Rahmat Dani Satria |
| author_sort | Usi Sukorini |
| collection | DOAJ |
| description | Abstract Deep vein thrombosis (DVT) is a clinically significant condition characterized by the formation of thrombi in deep venous structures, leading to high morbidity and potential mortality. Identifying reliable biomarkers for DVT risk prediction remains challenging due to the intricate genetic and molecular mechanisms underlying the disease. This study aims to investigate the best biomarker for DVT. Our study utilized genome-wide association studies (GWAS) findings coupled with a functional annotation scoring system to identify and prioritize genetic markers with strong associations to DVT. Furthermore, gene expression levels were analyzed to determine the most promising genetic markers. Several databases were utilized, including the GWAS Catalog, HaploReg 4.2, WebGestalt, Enrichr, and the GTEx Portal. Through the comprehensive analysis, we found 5 potential biomarkers and highlighted thrombomodulin (THBD) and Factor V (F5) as the best blood-based biomarkers. THBD and F5 genes were selected based on their elevated expression levels in blood and the presence of eQTLs. Functionally, THBD modulates coagulation via protein C activation, while F5 is pivotal in thrombin formation and clot stabilization, underscoring their mechanistic relevance to DVT pathogenesis, and rendering them suitable for non-invasive clinical assessment. Our findings emphasize the potential of genetic biomarkers to transform DVT risk assessment and support advancements in precision medicine for thrombotic disorders. |
| format | Article |
| id | doaj-art-d83f29d23da945cdb4fe3f2318441a2b |
| institution | OA Journals |
| issn | 2234-0742 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BioMed Central |
| record_format | Article |
| series | Genomics & Informatics |
| spelling | doaj-art-d83f29d23da945cdb4fe3f2318441a2b2025-08-20T01:51:59ZengBioMed CentralGenomics & Informatics2234-07422025-05-0123111210.1186/s44342-025-00047-2Genome-wide association study-driven identification of thrombomodulin and factor V as the best biomarker combination for deep vein thrombosisUsi Sukorini0Gisca Ajeng Widya Ninggar1Mohammad Hendra Setia Lesmana2Lalu Irham3Wirawan Adikusuma4Hegaria Rahmawati5Nur Imma Fatimah Harahap6Chiou-Feng Lin7Rahmat Dani Satria8Department of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah MadaDepartment of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah MadaDepartment of Nursing, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah MadaFaculty of Pharmacy, Ahmad Dahlan UniversityResearch Center for Computing, Research Organization for Electronics and Informatics, National Research and Innovation Agency (BRINPKU Muhammadiyah HospitalDepartment of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah MadaDepartment of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical UniversityDepartment of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah MadaAbstract Deep vein thrombosis (DVT) is a clinically significant condition characterized by the formation of thrombi in deep venous structures, leading to high morbidity and potential mortality. Identifying reliable biomarkers for DVT risk prediction remains challenging due to the intricate genetic and molecular mechanisms underlying the disease. This study aims to investigate the best biomarker for DVT. Our study utilized genome-wide association studies (GWAS) findings coupled with a functional annotation scoring system to identify and prioritize genetic markers with strong associations to DVT. Furthermore, gene expression levels were analyzed to determine the most promising genetic markers. Several databases were utilized, including the GWAS Catalog, HaploReg 4.2, WebGestalt, Enrichr, and the GTEx Portal. Through the comprehensive analysis, we found 5 potential biomarkers and highlighted thrombomodulin (THBD) and Factor V (F5) as the best blood-based biomarkers. THBD and F5 genes were selected based on their elevated expression levels in blood and the presence of eQTLs. Functionally, THBD modulates coagulation via protein C activation, while F5 is pivotal in thrombin formation and clot stabilization, underscoring their mechanistic relevance to DVT pathogenesis, and rendering them suitable for non-invasive clinical assessment. Our findings emphasize the potential of genetic biomarkers to transform DVT risk assessment and support advancements in precision medicine for thrombotic disorders.https://doi.org/10.1186/s44342-025-00047-2Deep vein thrombosisBiomarkersGenome-wide association studiesSingle nucleotide polymorphismsThrombomodulinFactor V |
| spellingShingle | Usi Sukorini Gisca Ajeng Widya Ninggar Mohammad Hendra Setia Lesmana Lalu Irham Wirawan Adikusuma Hegaria Rahmawati Nur Imma Fatimah Harahap Chiou-Feng Lin Rahmat Dani Satria Genome-wide association study-driven identification of thrombomodulin and factor V as the best biomarker combination for deep vein thrombosis Genomics & Informatics Deep vein thrombosis Biomarkers Genome-wide association studies Single nucleotide polymorphisms Thrombomodulin Factor V |
| title | Genome-wide association study-driven identification of thrombomodulin and factor V as the best biomarker combination for deep vein thrombosis |
| title_full | Genome-wide association study-driven identification of thrombomodulin and factor V as the best biomarker combination for deep vein thrombosis |
| title_fullStr | Genome-wide association study-driven identification of thrombomodulin and factor V as the best biomarker combination for deep vein thrombosis |
| title_full_unstemmed | Genome-wide association study-driven identification of thrombomodulin and factor V as the best biomarker combination for deep vein thrombosis |
| title_short | Genome-wide association study-driven identification of thrombomodulin and factor V as the best biomarker combination for deep vein thrombosis |
| title_sort | genome wide association study driven identification of thrombomodulin and factor v as the best biomarker combination for deep vein thrombosis |
| topic | Deep vein thrombosis Biomarkers Genome-wide association studies Single nucleotide polymorphisms Thrombomodulin Factor V |
| url | https://doi.org/10.1186/s44342-025-00047-2 |
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