Publications by authors named "P-E Morange"
Background: Antithrombin, PC (protein C), and PS (protein S) are circulating natural anticoagulant proteins that regulate hemostasis and of which partial deficiencies are causes of venous thromboembolism. Previous genetic association studies involving antithrombin, PC, and PS were limited by modest sample sizes or by being restricted to candidate genes. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, we meta-analyzed across ancestries the results from 10 genome-wide association studies of plasma levels of antithrombin, PC, PS free, and PS total.
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- Fibrinogen is crucial for blood clotting and inflammation, and its circulating levels may be influenced by differences in DNA methylation at specific CpG sites.
- An epigenome-wide association study analyzed blood DNA methylation and fibrinogen levels in over 18,000 diverse participants, revealing significant associations through advanced statistical models.
- The study identified a total of 83 replicated CpG sites linked to fibrinogen, highlighting genes involved in inflammation, with many associations being affected but still significant after adjusting for C-reactive protein (CRP) levels.
Background: Venous thromboembolism (VTE) is a life-threatening vascular event with environmental and genetic determinants. Recent VTE genome-wide association studies (GWAS) meta-analyses involved nearly 30 000 VTE cases and identified up to 40 genetic loci associated with VTE risk, including loci not previously suspected to play a role in hemostasis. The aim of our research was to expand discovery of new genetic loci associated with VTE by using cross-ancestry genomic resources.
View Article and Find Full Text PDFObjective: Deep vein thrombosis and pulmonary embolism referred as venous thromboembolism (VTE) are a common cause of morbidity and mortality. Plasma from healthy controls or individuals who have experienced a VTE were analyzed using metabolomics to characterize biomarkers and metabolic systems of patients with VTE. Approach and Results: Polar metabolite and lipidomic profiles from plasma collected 3 months after an incident VTE were obtained using liquid chromatography mass spectrometry.
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- - The study investigates the genetic factors influencing plasma levels of Factor VIII (FVIII) and von Willebrand factor (VWF), which are linked to both clotting disorders and thrombosis risk, using data from over 46,000 individuals across various ethnic backgrounds.
- - Researchers discovered 13 new genetic associations with FVIII and VWF levels, including 7 associated with FVIII and 11 with VWF, extending the knowledge beyond previously known variants. Functional tests supported most of these associations.
- - The analysis suggests that higher plasma levels of FVIII may contribute to increased risk of venous thrombosis and coronary artery disease, while elevated VWF levels might heighten the risk of ischemic stroke, highlighting the potential for these proteins
Background: Genetics plays an important role in venous thromboembolism (VTE). Factor V Leiden (FVL or rs6025) and prothrombin gene G20210A (PT or rs1799963) are the genetic variants currently tested for VTE risk assessment. We hypothesized that primary VTE risk assessment can be improved by using genetic risk scores with more genetic markers than just FVL-rs6025 and prothrombin gene PT-rs1799963.
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- Researchers analyzed data from 14 studies involving nearly 27,000 participants to find genetic factors influencing the levels of tissue plasminogen activator (tPA), a key enzyme in blood clot breakdown.
- They identified three significant genetic loci associated with tPA levels: one linked to the STXBP5 gene on chromosome 6, another near the PLAT gene on chromosome 8, and a third related to the STX2 gene on chromosome 12.
- Functional tests showed that silencing STXBP5 reduces tPA release from cells, while silencing STX2 increases it, suggesting these genes play important roles in regulating tPA levels.