Heritability of hemostasis phenotypes and their correlation with type 2 diabetes status in Mexican Americans.
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 < or = 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.
Warren
Diane M
DM
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA.
Soria
José Manuel
JM
Souto
Juan Carlos
JC
Comuzzie
Anthony
A
Fontcuberta
Jordi
J
Blangero
John
J
MacCluer
Jean W
JW
Almasy
Laura
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001779:Blood Coagulation Factors / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D006487:Hemostasis / Q000235:genetics*; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D017058:Mexican Americans / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors; D013781:Texas
D001779:Blood Coagulation Factors