Identification of quantitative trait loci for fibrin clot phenotypes: the EuroCLOT study

Frances M K Williams; Angela M Carter; Bernet Kato; Mario Falchi; Lise Bathum; Gabriela Surdulescu; Kirsten Ohm Kyvik; Aarno Palotie; Tim D Spector; Peter J Grant; EuroCLOT Investigators

doi:10.1161/ATVBAHA.108.178103

Identification of quantitative trait loci for fibrin clot phenotypes: the EuroCLOT study

Frances M K Williams, Angela M Carter, Bernet Kato, Mario Falchi, Lise Bathum, Gabriela Surdulescu, Kirsten Ohm Kyvik, Aarno Palotie, Tim D Spector, Peter J Grant, EuroCLOT Investigators

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

OBJECTIVE: Fibrin makes up the structural basis of an occlusive arterial thrombus, and variability in fibrin phenotype relates to cardiovascular risk. The aims of the current study from the EU consortium EuroCLOT were to (1) determine the heritability of fibrin phenotypes and (2) identify QTLs associated with fibrin phenotypes.

METHODS AND RESULTS: 447 dizygotic (DZ) and 460 monozygotic (MZ) pairs of healthy UK white female twins and 199 DZ twin pairs from Denmark were studied. D-dimer, an indicator of fibrin turnover, was measured by ELISA and measures of clot formation, morphology, and lysis were determined by turbidimetric assays. Heritability estimates and genome-wide linkage analysis were performed. Estimates of heritability for d-dimer and turbidometric variables were in the range 17% to 46%, with highest levels for maximal absorbance which provides an estimate of clot density. Genome-wide linkage analysis revealed 6 significant regions with LOD >3 on 5 chromosomes (5, 6, 9, 16, and 17).

CONCLUSIONS: The results indicate a significant genetic contribution to variability in fibrin phenotypes and highlight regions in the human genome which warrant further investigation in relation to ischemic cardiovascular disorders and their therapy.

Original language	English
Pages (from-to)	600-5
Number of pages	6
Journal	Arteriosclerosis, Thrombosis, and Vascular Biology
Volume	29
Issue number	4
DOIs	https://doi.org/10.1161/ATVBAHA.108.178103
Publication status	Published - Apr 2009

Keywords

Adult
Blood Coagulation
Cardiovascular Diseases
Denmark
Female
Fibrin Fibrinogen Degradation Products
Genetic Predisposition to Disease
Genome-Wide Association Study
Great Britain
Humans
Linkage Disequilibrium
Middle Aged
Phenotype
Quantitative Trait Loci
Quantitative Trait, Heritable
Registries
Thrombosis
Twins, Dizygotic
Twins, Monozygotic

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1161/ATVBAHA.108.178103

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Williams, F. M. K., Carter, A. M., Kato, B., Falchi, M., Bathum, L., Surdulescu, G., Kyvik, K. O., Palotie, A., Spector, T. D., Grant, P. J., & EuroCLOT Investigators (2009). Identification of quantitative trait loci for fibrin clot phenotypes: the EuroCLOT study. Arteriosclerosis, Thrombosis, and Vascular Biology, 29(4), 600-5. https://doi.org/10.1161/ATVBAHA.108.178103

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abstract = "OBJECTIVE: Fibrin makes up the structural basis of an occlusive arterial thrombus, and variability in fibrin phenotype relates to cardiovascular risk. The aims of the current study from the EU consortium EuroCLOT were to (1) determine the heritability of fibrin phenotypes and (2) identify QTLs associated with fibrin phenotypes.METHODS AND RESULTS: 447 dizygotic (DZ) and 460 monozygotic (MZ) pairs of healthy UK white female twins and 199 DZ twin pairs from Denmark were studied. D-dimer, an indicator of fibrin turnover, was measured by ELISA and measures of clot formation, morphology, and lysis were determined by turbidimetric assays. Heritability estimates and genome-wide linkage analysis were performed. Estimates of heritability for d-dimer and turbidometric variables were in the range 17% to 46%, with highest levels for maximal absorbance which provides an estimate of clot density. Genome-wide linkage analysis revealed 6 significant regions with LOD >3 on 5 chromosomes (5, 6, 9, 16, and 17).CONCLUSIONS: The results indicate a significant genetic contribution to variability in fibrin phenotypes and highlight regions in the human genome which warrant further investigation in relation to ischemic cardiovascular disorders and their therapy.",

keywords = "Adult, Blood Coagulation, Cardiovascular Diseases, Denmark, Female, Fibrin Fibrinogen Degradation Products, Genetic Predisposition to Disease, Genome-Wide Association Study, Great Britain, Humans, Linkage Disequilibrium, Middle Aged, Phenotype, Quantitative Trait Loci, Quantitative Trait, Heritable, Registries, Thrombosis, Twins, Dizygotic, Twins, Monozygotic",

author = "Williams, {Frances M K} and Carter, {Angela M} and Bernet Kato and Mario Falchi and Lise Bathum and Gabriela Surdulescu and Kyvik, {Kirsten Ohm} and Aarno Palotie and Spector, {Tim D} and Grant, {Peter J} and {EuroCLOT Investigators}",

year = "2009",

month = apr,

doi = "10.1161/ATVBAHA.108.178103",

language = "English",

volume = "29",

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journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",

publisher = "Lippincott Williams and Wilkins",

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T1 - Identification of quantitative trait loci for fibrin clot phenotypes

T2 - the EuroCLOT study

AU - Williams, Frances M K

AU - Carter, Angela M

AU - Kato, Bernet

AU - Falchi, Mario

AU - Bathum, Lise

AU - Surdulescu, Gabriela

AU - Kyvik, Kirsten Ohm

AU - Palotie, Aarno

AU - Spector, Tim D

AU - Grant, Peter J

AU - EuroCLOT Investigators

PY - 2009/4

Y1 - 2009/4

N2 - OBJECTIVE: Fibrin makes up the structural basis of an occlusive arterial thrombus, and variability in fibrin phenotype relates to cardiovascular risk. The aims of the current study from the EU consortium EuroCLOT were to (1) determine the heritability of fibrin phenotypes and (2) identify QTLs associated with fibrin phenotypes.METHODS AND RESULTS: 447 dizygotic (DZ) and 460 monozygotic (MZ) pairs of healthy UK white female twins and 199 DZ twin pairs from Denmark were studied. D-dimer, an indicator of fibrin turnover, was measured by ELISA and measures of clot formation, morphology, and lysis were determined by turbidimetric assays. Heritability estimates and genome-wide linkage analysis were performed. Estimates of heritability for d-dimer and turbidometric variables were in the range 17% to 46%, with highest levels for maximal absorbance which provides an estimate of clot density. Genome-wide linkage analysis revealed 6 significant regions with LOD >3 on 5 chromosomes (5, 6, 9, 16, and 17).CONCLUSIONS: The results indicate a significant genetic contribution to variability in fibrin phenotypes and highlight regions in the human genome which warrant further investigation in relation to ischemic cardiovascular disorders and their therapy.

AB - OBJECTIVE: Fibrin makes up the structural basis of an occlusive arterial thrombus, and variability in fibrin phenotype relates to cardiovascular risk. The aims of the current study from the EU consortium EuroCLOT were to (1) determine the heritability of fibrin phenotypes and (2) identify QTLs associated with fibrin phenotypes.METHODS AND RESULTS: 447 dizygotic (DZ) and 460 monozygotic (MZ) pairs of healthy UK white female twins and 199 DZ twin pairs from Denmark were studied. D-dimer, an indicator of fibrin turnover, was measured by ELISA and measures of clot formation, morphology, and lysis were determined by turbidimetric assays. Heritability estimates and genome-wide linkage analysis were performed. Estimates of heritability for d-dimer and turbidometric variables were in the range 17% to 46%, with highest levels for maximal absorbance which provides an estimate of clot density. Genome-wide linkage analysis revealed 6 significant regions with LOD >3 on 5 chromosomes (5, 6, 9, 16, and 17).CONCLUSIONS: The results indicate a significant genetic contribution to variability in fibrin phenotypes and highlight regions in the human genome which warrant further investigation in relation to ischemic cardiovascular disorders and their therapy.

KW - Adult

KW - Blood Coagulation

KW - Cardiovascular Diseases

KW - Denmark

KW - Female

KW - Fibrin Fibrinogen Degradation Products

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Great Britain

KW - Humans

KW - Linkage Disequilibrium

KW - Middle Aged

KW - Phenotype

KW - Quantitative Trait Loci

KW - Quantitative Trait, Heritable

KW - Registries

KW - Thrombosis

KW - Twins, Dizygotic

KW - Twins, Monozygotic

U2 - 10.1161/ATVBAHA.108.178103

DO - 10.1161/ATVBAHA.108.178103

M3 - Article

C2 - 19150881

VL - 29

SP - 600

EP - 605

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

IS - 4

ER -

Identification of quantitative trait loci for fibrin clot phenotypes: the EuroCLOT study

Abstract

Keywords

UN SDGs

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