Genetic determinants of hemostasis phenotypes in Spanish families

Juan Carlos Souto, Laura Almasy, Montserrat Borrell, Merce Garí, Elisabet Martínez, José Mateo, William H. Stone, John Blangero, Jordi Fontcuberta

Research output: Contribution to journalArticle

219 Citations (Scopus)

Abstract

Background - Recent studies have described genetic mutations that affect the risk of thrombosis as a result of abnormal levels of such hemostatic parameters as protein C, protein S, and the activated protein C resistance ratio. Although these mutations suggest that genes play a part in determining variability in some hemostasis-related phenotypes, the relative importance of genetic influences on these traits has not been evaluated. Methods and Results - The relative contributions of genetic and environmental influences to a panel of hemostasis-related phenotypes were assessed in a sample of 397 individuals in 21 extended pedigrees. The effects of measured covariates (sex, age, smoking, and exogenous sex hormones), genes, and environmental variables shared by members of a household were quantified for 27 hemostasis- related measures. All of these phenotypes showed significant genetic contributions, with the majority of heritabilities ranging between 22% and 55% of the residual phenotypic variance after correction for covariate effects. Activated protein C resistance ratio, activated partial thromboplastin time, and Factor XII showed the strongest heritabilities, with 71.3%, 83.0%, and 67.3%, respectively, of the residual phenotypic variation attributable to genetic effects. Conclusions - These results clearly demonstrate the importance of genetic factors in determining variation in hemostasis-related phenotypes that are components of the coagulation and fibrinolysis pathways and that have been implicated in risk for thrombosis. The presence of such strong genetic effects suggests that it will be possible to localize previously unknown genes that influence quantitative variation in these hemostasis-related phenotypes that may contribute to risk for thrombosis.

Original languageEnglish (US)
Pages (from-to)1546-1551
Number of pages6
JournalCirculation
Volume101
Issue number13
StatePublished - Apr 4 2000
Externally publishedYes

Fingerprint

Hemostasis
Phenotype
Activated Protein C Resistance
Thrombosis
Genes
Factor XII
Mutation
Partial Thromboplastin Time
Protein S
Gonadal Steroid Hormones
Fibrinolysis
Hemostatics
Pedigree
Protein C
Smoking

Keywords

  • Coagulation
  • Epidemiology
  • Fibrinolysis
  • Genetics
  • Thrombosis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Souto, J. C., Almasy, L., Borrell, M., Garí, M., Martínez, E., Mateo, J., ... Fontcuberta, J. (2000). Genetic determinants of hemostasis phenotypes in Spanish families. Circulation, 101(13), 1546-1551.

Genetic determinants of hemostasis phenotypes in Spanish families. / Souto, Juan Carlos; Almasy, Laura; Borrell, Montserrat; Garí, Merce; Martínez, Elisabet; Mateo, José; Stone, William H.; Blangero, John; Fontcuberta, Jordi.

In: Circulation, Vol. 101, No. 13, 04.04.2000, p. 1546-1551.

Research output: Contribution to journalArticle

Souto, JC, Almasy, L, Borrell, M, Garí, M, Martínez, E, Mateo, J, Stone, WH, Blangero, J & Fontcuberta, J 2000, 'Genetic determinants of hemostasis phenotypes in Spanish families', Circulation, vol. 101, no. 13, pp. 1546-1551.
Souto JC, Almasy L, Borrell M, Garí M, Martínez E, Mateo J et al. Genetic determinants of hemostasis phenotypes in Spanish families. Circulation. 2000 Apr 4;101(13):1546-1551.
Souto, Juan Carlos ; Almasy, Laura ; Borrell, Montserrat ; Garí, Merce ; Martínez, Elisabet ; Mateo, José ; Stone, William H. ; Blangero, John ; Fontcuberta, Jordi. / Genetic determinants of hemostasis phenotypes in Spanish families. In: Circulation. 2000 ; Vol. 101, No. 13. pp. 1546-1551.
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abstract = "Background - Recent studies have described genetic mutations that affect the risk of thrombosis as a result of abnormal levels of such hemostatic parameters as protein C, protein S, and the activated protein C resistance ratio. Although these mutations suggest that genes play a part in determining variability in some hemostasis-related phenotypes, the relative importance of genetic influences on these traits has not been evaluated. Methods and Results - The relative contributions of genetic and environmental influences to a panel of hemostasis-related phenotypes were assessed in a sample of 397 individuals in 21 extended pedigrees. The effects of measured covariates (sex, age, smoking, and exogenous sex hormones), genes, and environmental variables shared by members of a household were quantified for 27 hemostasis- related measures. All of these phenotypes showed significant genetic contributions, with the majority of heritabilities ranging between 22{\%} and 55{\%} of the residual phenotypic variance after correction for covariate effects. Activated protein C resistance ratio, activated partial thromboplastin time, and Factor XII showed the strongest heritabilities, with 71.3{\%}, 83.0{\%}, and 67.3{\%}, respectively, of the residual phenotypic variation attributable to genetic effects. Conclusions - These results clearly demonstrate the importance of genetic factors in determining variation in hemostasis-related phenotypes that are components of the coagulation and fibrinolysis pathways and that have been implicated in risk for thrombosis. The presence of such strong genetic effects suggests that it will be possible to localize previously unknown genes that influence quantitative variation in these hemostasis-related phenotypes that may contribute to risk for thrombosis.",
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AB - Background - Recent studies have described genetic mutations that affect the risk of thrombosis as a result of abnormal levels of such hemostatic parameters as protein C, protein S, and the activated protein C resistance ratio. Although these mutations suggest that genes play a part in determining variability in some hemostasis-related phenotypes, the relative importance of genetic influences on these traits has not been evaluated. Methods and Results - The relative contributions of genetic and environmental influences to a panel of hemostasis-related phenotypes were assessed in a sample of 397 individuals in 21 extended pedigrees. The effects of measured covariates (sex, age, smoking, and exogenous sex hormones), genes, and environmental variables shared by members of a household were quantified for 27 hemostasis- related measures. All of these phenotypes showed significant genetic contributions, with the majority of heritabilities ranging between 22% and 55% of the residual phenotypic variance after correction for covariate effects. Activated protein C resistance ratio, activated partial thromboplastin time, and Factor XII showed the strongest heritabilities, with 71.3%, 83.0%, and 67.3%, respectively, of the residual phenotypic variation attributable to genetic effects. Conclusions - These results clearly demonstrate the importance of genetic factors in determining variation in hemostasis-related phenotypes that are components of the coagulation and fibrinolysis pathways and that have been implicated in risk for thrombosis. The presence of such strong genetic effects suggests that it will be possible to localize previously unknown genes that influence quantitative variation in these hemostasis-related phenotypes that may contribute to risk for thrombosis.

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