Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Meta-analysis of Genome-Wide-Association Sudies for plasma Factor XI

ABSTRACT: Coagulation factor XI (FXI) has become increasingly interesting for its role in pathogenesis of thrombosis. We performed a genome-wide association study (GWAS) for plasma FXI levels, using novel data imputed to the 1000 Genomes reference panel. Individual GWAS analyses, including a total of 16,169 European individuals from the ARIC, GHS, MARTHA and PROCARDIS studies, were meta-analyzed, and results are presented here.

PROVIDER: EGAS00001002123 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Similar Datasets

GENEVA GWAS of Venous Thrombosis

Project description:GENEVA GWAS of Venous Thrombosis

| PRJNA75937 | ENA

Homo sapiens

Project description:GENEVA GWAS of Venous Thrombosis

| PRJNA75939 | ENA

Tumor-derived Tissue Factor Activates Coagulation and Enhances Thrombosis in a Mouse Xenograft Model of Human Pancreatic Cancer

Project description:Cancer patients often have an activated clotting system and are at increased risk for venous thrombosis. In this study, we analyzed tissue factor (TF) expression in four different human pancreatic tumor cell lines for the purpose of producing derivative tumors in vivo. We found that two of the lines expressed TF and released TF-positive microparticles (MPs) into the culture medium. The majority of TF protein in the culture medium was associated with MPs. Importantly, only TF-positive cell lines activated coagulation in nude mice, and this activation was abolished by an anti-human TF antibody. Of the two TF-positive lines only one produced detectable levels of human MP TF activity in the plasma when grown orthotopically in nude mice. Surprisingly, <5% of human TF protein in plasma from tumor-bearing mice was associated with MPs. Mice with TF-positive tumors and elevated levels of circulating TF-positive MPs had increased thrombosis in a saphenous vein model. In contrast, we observed no difference in thrombus weight between tumor bearing and control mice in an inferior vena cava stenosis model. Our studies suggest that in a xenograft mouse model tumor TF activates coagulation, whereas TF on circulating MPs may trigger venous thrombosis.

2012-07-12 | GSE37575 | GEO

lnFXI_metaanalysis_summarydata

Project description:Summary data from Meta-analysis of Genome-Wide-Association Studies for plasma levels of Coagulation Factor XI (FXI)

| EGAD00010001141 | EGA

FXI GWAS meta-analysis

Project description:Meta-analysis of Genome-Wide-Association Sudies for plasma Factor XI

| PRJEB17692 | ENA

Self-anticoagulant sponges for whole blood auto-transfusion and its mechanism of coagulation factor inactivation

Project description:Clinical use of intraoperative auto-transfusion requires the removal of platelets and plasma proteins due to the pump-based suction and water-soluble anticoagulant administration, which causes dilutional coagulopathy. Herein, we develop a carboxylated and sulfonated heparin-mimetic polymer-modified sponge that could spontaneously adsorb blood (1.149 kg/m-2 s-1/2) along with instantaneous anticoagulation. We demonstrate that intrinsic coagulation factors (especially XI) are inactivated by adsorption to the sponge surface, while inactivation of thrombin in the sponge-treated plasma effectively inhibits the common coagulation pathway. Benefiting from the multiple inhibitory effects of sponge on coagulation enzymes and calcium depletion, the whole blood auto-transfusion in trauma-induced hemorrhage is unprecedentedly realized. The transfusion of collected blood favors faster recovery of hemostasis compared to traditional heparinized blood in an animal model. Our work not only develops a safe and convenient approach for whole blood auto-transfusion, but also provides the mechanism of action of self-anticoagulant heparin-mimetic polymer-modified surfaces.

2023-07-23 | PXD044005 | Pride

Thrombin activation of the factor XI dimer is a multi-staged process for each subunit

Project description:Factor XI (FXI) is a protein in the intrinsic coagulation pathway that can be activated by two enzymes. In hemostasis, FXI is activated by thrombin, while FXIIa-mediated activation of FXI is thought to be prothrombotic. The interactions of these enzymes with FXI are poorly understood due to their transient nature which is difficult to study. Here, we applied crosslinking mass spectrometry (XLMS) and molecular dynamics simulations to investigate the binding interface between thrombin and FXI as well as the dynamics underlying the activation of FXI. From the experimental data we were able to construct the FXI homodimer as well as locate the binding interface of thrombin on the light chain of FXI. As this placed thrombin distal from both the activation site as well as the apple 1 domain that thrombin is known to interact with, we applied molecular dynamics simulations to investigate the chain of events after binding. From the resulting model, we hypothesize that the activation of FXI is a multi-staged procedure where thrombin first binds to Pro520 on FXI, after which it migrates towards the activation site by first engaging the apple 1 domain and finally Arg378. We validated the results with known mutation sites on FXI and additionally found that Pro520 is conserved in PK and enables binding of thrombin to this enzyme even though it cannot be activated by it. This interaction points a way for future interventions for bleeding and thrombosis.

2024-02-05 | PXD039489 | Pride

Homo sapiens

Project description:Regulation of Coagulation Factor XI expression by MicroRNAs in the Human Liver

| PRJNA260525 | ENA

Absence of COVID-19-associated Changes in Coagulation and Thrombosis in the Ferret Model

Project description:Many patients who are diagnosed with coronavirus disease 2019 (COVID-19) suffer from venous thromboembolic complications despite the use of stringent anticoagulant prophylaxis. Studies on the exact mechanism(s) underlying thrombosis in COVID-19 are limited as animal models commonly used to study venous thrombosis pathophysiology (i.e. rats and mice) are naturally not susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Ferrets are susceptible to SARS-CoV-2 infection, successfully used to study virus transmission, and were previously used to study activation of coagulation and thrombosis during influenza virus infection. Here, we used plasma and lung material from SARS-CoV-2-inoculated ferrets to explore their use in studying COVID-19-associated changes in coagulation and thrombosis. Lungs of ferrets inoculated intranasally with SARS-CoV-2 demonstrated alveolar septa that were mildly expanded by macrophages, and diffuse interstitial histiocytic pneumonia. However, no macroscopical or microscopical evidence of vascular thrombosis in the lungs of SARS-CoV-2-inoculated ferrets was found. Longitudinal plasma profiling using a mass spectrometry-based approach revealed minor differences in plasma protein profiles in SARS-CoV-2-inoculated ferrets up to 2 weeks post-infection. Apart from fibrinogen, the majority of plasma coagulation factors were stable and demonstrated a low coefficient of variation. We conclude that while ferrets are an essential and well-suited animal model to study SARS-CoV-2 transmission, their use to study SARS-CoV-2-related changes relevant to thrombotic disease is limited.

2022-07-19 | PXD027582 | Pride

Biological constraints on GWAS SNPs at suggestive significance thresholds reveal true BMI loci [hMSC_adipocytes_atacseq]

Project description:We investigated whether intersecting functional genomic data (ATAC-seq + promoter focused Capture C) with increasingly powered publically available GWAS for Body Mass Index and Waist to Hip Ratio could identify additional true postiive subsignficant signals (5x10-8< P value < 5x10-4) without increasing the GWAS sample size

2021-01-16 | GSE164745 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data