TY - JOUR
T1 - Thromboplastin-thrombomodulin-mediated time and serum folate levels are genetically correlated with the risk of thromboembolic disease
T2 - Results from the GAIT Project
AU - Souto, Juan Carlos
AU - Almasy, Laura
AU - Borrell, Montserrat
AU - Stone, William H.
AU - Blanco-Vaca, Francisco
AU - Soria, José Manuel
AU - Blangero, John
AU - Fontcuberta, Jordi
PY - 2002
Y1 - 2002
N2 - The GAIT (Genetic Analysis of Idiopathic Thrombophilia) Project is a family-based study dedicated to elucidating the genetic basis of hemostasis-related phenotypes and thrombosis risk. In this paper, we have examined several lesser-studied hemostasis-related phenotypes in the 21 GAIT families: levels of vitamin B12, serum folate, whole blood folate, α2-antiplasmin, prekallikrein, β2-glycoprotein I, soluble P-selectin, factor XIII A and B subunits and a new coagulation measurement based on thromboplastin time in the presence or absence of thrombomodulin. Using the variance component method, we estimated the relative contributions of genetic and environmental influences on these phenotypes. In addition, we calculated the genetic correlations between thrombosis risk and each of these phenotypes. All 12 phenotypes showed significant genetic contributions with genes accounting for 22% to 78% fo the variance after correction for covariate effects. Four phenotypes (three traits involving thromboplastin-thrombomodulin mediated coagulation time and serum folate) exhibited significant genetic correlations with thrombosis. Thus, some of the genes that influence quantitative variation in these physiological phenotypes also influence the risk of thrombosis. The high heritabilities and significant genetic correlations between thrombosis and some risk factors suggest that joint consideration of correlated quantitative phenotypes will aid in identifying susceptibility genes.
AB - The GAIT (Genetic Analysis of Idiopathic Thrombophilia) Project is a family-based study dedicated to elucidating the genetic basis of hemostasis-related phenotypes and thrombosis risk. In this paper, we have examined several lesser-studied hemostasis-related phenotypes in the 21 GAIT families: levels of vitamin B12, serum folate, whole blood folate, α2-antiplasmin, prekallikrein, β2-glycoprotein I, soluble P-selectin, factor XIII A and B subunits and a new coagulation measurement based on thromboplastin time in the presence or absence of thrombomodulin. Using the variance component method, we estimated the relative contributions of genetic and environmental influences on these phenotypes. In addition, we calculated the genetic correlations between thrombosis risk and each of these phenotypes. All 12 phenotypes showed significant genetic contributions with genes accounting for 22% to 78% fo the variance after correction for covariate effects. Four phenotypes (three traits involving thromboplastin-thrombomodulin mediated coagulation time and serum folate) exhibited significant genetic correlations with thrombosis. Thus, some of the genes that influence quantitative variation in these physiological phenotypes also influence the risk of thrombosis. The high heritabilities and significant genetic correlations between thrombosis and some risk factors suggest that joint consideration of correlated quantitative phenotypes will aid in identifying susceptibility genes.
KW - Coagulation
KW - Family-based studies
KW - Genetics
KW - Heritability
KW - Thrombosis
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UR - http://www.scopus.com/inward/citedby.url?scp=0036148263&partnerID=8YFLogxK
U2 - 10.1055/s-0037-1612945
DO - 10.1055/s-0037-1612945
M3 - Article
C2 - 11848458
AN - SCOPUS:0036148263
SN - 0340-6245
VL - 87
SP - 68
EP - 73
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 1
ER -