The goal of this project is to test for association between candidate polymorphisms for hemostatic factors and cardiovascular-related outcomes in family data. The data consist of 717 observations (87 pedigrees) from Korea. The families were ascertained through probands undergoing elective coronary arteriography as part of the Yonsei Coronary Artery Disease Study. Data collection is still ongoing. Age, sex, cigarette smoking, alcohol consumption among others covariates were obtained through a questionnaire. The following traits were measured: BMI levels of hemostatic factors (clotting factors VII and fibrinogen and plasminogen activator inhibitor ? 1 or PAI-1), triglycerides, total and HDL cholesterol, and blood pressure. The individual and family identification numbers were randomized before analysis to respect confidentiality. The Regression of Offspring on Mid-Parent (ROMP) method was used to estimate overall trait heritability and locus-specific heritability, and to test for association between the traits and the candidate polymorphisms. Clotting factor VII, PAI-1 and HDL cholesterol and triglyceride showed heritability estimates over 45% adjustment (p-value < 0.0001). The estimates for total cholesterol, fibrinogen, BMI, systolic and diastolic blood pressure were 32 ? 8%, 14 ? 10%, 20 ? 14%, 27 ? 11%, and 9 ? 11%, respectively. Clotting factor fibrinogen and PAI-1 showed the strongest association (locus-specific heritability estimate close to 3 ? 1% with a p-value smaller than 0.01) with 3 linked polymorphisms in the fibrinogen gene. Clotting factor VII was associated with a candidate polymorphism for which previous studies reported associations (locus-specific heritability estimate of 1.4 ? 0.6%, p-value = 0.027). Although significant associations were found, these polymorphisms account for only a small percentage of the heritability of the traits (3-7%). This suggests that several other genes and/or shared familial and environmental factors may be responsible for the high heritability of these traits.
