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Blood
- Source :
- Blood, Blood, American Society of Hematology, 2020, 136 (26), pp.3062-3069. ⟨10.1182/blood.2019004781⟩, Blood, 136(26), 3062-3069. American Society of Hematology
- Publication Year :
- 2020
- Publisher :
- HAL CCSD, 2020.
-
Abstract
- Fibrinogen is a key component of the coagulation cascade, and variation in its circulating levels may contribute to thrombotic diseases, such as venous thromboembolism (VTE) and ischemic stroke. Gamma prime (γ′) fibrinogen is an isoform of fibrinogen that has anticoagulant properties. We applied 2-sample Mendelian randomization (MR) to estimate the causal effect of total circulating fibrinogen and its isoform, γ′ fibrinogen, on risk of VTE and ischemic stroke subtypes using summary statistics from genome-wide association studies. Genetic instruments for γ′ fibrinogen and total fibrinogen were selected, and the inverse-variance weighted MR approach was used to estimate causal effects in the main analysis, complemented by sensitivity analyses that are more robust to the inclusion of pleiotropic variants, including MR-Egger, weighted median MR, and weighted mode MR. The main inverse-variance weighted MR estimates based on a combination of 16 genetic instruments for γ′ fibrinogen and 75 genetic instruments for total fibrinogen indicated a protective effect of higher γ′ fibrinogen and higher total fibrinogen on VTE risk. There was also a protective effect of higher γ′ fibrinogen levels on cardioembolic and large artery stroke risk. Effect estimates were consistent across sensitivity analyses. Our results provide evidence to support effects of genetically determined γ′ fibrinogen on VTE and ischemic stroke risk. Further research is needed to explore mechanisms underlying these effects and their clinical applications.
- Subjects :
- Male
0301 basic medicine
LOCI
Genome-wide association study
030204 cardiovascular system & hematology
Fibrinogen
Biochemistry
Thrombosis and Hemostasis
0302 clinical medicine
SPLICE VARIANT
Risk Factors
1102 Cardiorespiratory Medicine and Haematology
Hematology
Anticoagulant
GENETIC-VARIATION
Mendelian Randomization Analysis
ASSOCIATION
Venous Thromboembolism
3. Good health
Coagulation
Cardiology
Female
Life Sciences & Biomedicine
medicine.drug
medicine.medical_specialty
medicine.drug_class
CHARGE Inflammation Working Group
Immunology
COAGULATION
ATHEROSCLEROSIS RISK
INVENT Consortium
GENOTYPE IMPUTATION
03 medical and health sciences
INFLAMMATION
MEGASTROKE consortium of the International Stroke Genetics Consortium (ISGC)
Internal medicine
Mendelian randomization
medicine
Humans
METAANALYSIS
Ischemic Stroke
Genetic association
Science & Technology
business.industry
Genetic Variation
1103 Clinical Sciences
Cell Biology
030104 developmental biology
CHAIN
1114 Paediatrics and Reproductive Medicine
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
business
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 00064971 and 15280020
- Database :
- OpenAIRE
- Journal :
- Blood, Blood, American Society of Hematology, 2020, 136 (26), pp.3062-3069. ⟨10.1182/blood.2019004781⟩, Blood, 136(26), 3062-3069. American Society of Hematology
- Accession number :
- edsair.doi.dedup.....bb7e77bb7c2fea0fc3aab46c442c555f