Heritability of hemostasis phenotypes and their correlation with type 2 diabetes status in Mexican Americans

Diane M. Warren, José Manuel Soria, Juan Carlos Souto, Anthony Comuzzie, Jordi Fontcuberta, John Blangero, Jean W. Maccluer, Laura Almasy

    Research output: Contribution to journalArticlepeer-review

    22 Scopus citations

    Abstract

    Hypercoagulation often occurs in type 2 diabetes, suggesting pleiotropy of the genes that influence disease liability and hemostasis-related phenotypes. To better understand the relationship between hemostasis and diabetes, we first used maximum-likelihood methods to estimate the relative contribution of additive genetic, measured environmental, and shared household effects to the normal variance of 16 hemostasis-related traits in 813 individuals participating in the San Antonio Family Heart Study. We estimated moderate to high heritabilities (0.20-0.60) for each phenotype. Von Willebrand factor (VWF), thrombin activatable fibrinolysis inhibitor, activated protein C (APC) ratio, factor V, and prothrombin time had heritabilities greater than 0.50. The correlation between type 2 diabetes status and the hemostasis-related traits was then partitioned into genetic and environmental components using bivariate variance-components methods. Significant (p ≤ 0.05) positive genetic correlations (0.37-0.51) occurred with factors II and VIII, VWF, total protein S (tPS), and tissue factor pathway inhibitor. Significant negative genetic correlations were estimated for activated partial thromboplastin time (-0.49) and APC ratio (-0.38). By contrast, significant environmental correlations occurred only with factor II (-0.40) and tPS (-0.31). Our results suggest that genes are important contributors to the normal variation in hemostasis-related traits and that genes influencing hemostasis-related traits pleiotropically influence diabetes risk.

    Original languageEnglish (US)
    Pages (from-to)1-15
    Number of pages15
    JournalHuman Biology
    Volume77
    Issue number1
    DOIs
    StatePublished - Feb 2005

    Keywords

    • Clotting factors
    • Diabetes
    • Family study
    • Hemostasis
    • Hemostasis-related traits
    • Heritability Mexican Americans
    • Protein C
    • Protein S
    • Prothrombin time
    • San Antonio Family Heart Study
    • Thrombin activatable fibrinolysis inhibitor (TAFI)

    ASJC Scopus subject areas

    • Ecology, Evolution, Behavior and Systematics
    • Genetics
    • Genetics(clinical)

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