title: Thromboplastin-thrombomodulin-mediated time and serum folate levels are genetically correlated with the risk of thromboembolic disease: results from the GAIT project.
abstract: 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 B 12, serum folate, whole blood folate, alpha2-antiplasmin, prekallikrein, beta2-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% of 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.
authors.affiliation: Unitat d'Hemostàsia i Trombosi, Departament d'Hematologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. jsouto@hsp.santpau.es
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Souto
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.forename: Montserrat
authors.initials: M
authors.lastname: Borrell
authors.forename: William H
authors.initials: WH
authors.lastname: Stone
authors.forename: Francisco
authors.initials: F
authors.lastname: Blanco-Vaca
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Soria
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.forename: Jordi
authors.initials: J
authors.lastname: Fontcuberta
mesh_terms: D000328:Adult; D001780:Blood Coagulation Tests; D015897:Comorbidity; D003278:Contraceptives, Oral, Hormonal / Q000494:pharmacology; D005176:Factor XIII / Q000032:analysis; D005260:Female; D005492:Folic Acid / Q000097:blood*; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010641:Phenotype; D012307:Risk Factors; D012907:Smoking / Q000097:blood; D013030:Spain / Q000453:epidemiology; D018180:Thrombomodulin / Q000502:physiology*; D019851:Thrombophilia / Q000097:blood / Q000453:epidemiology* / Q000235:genetics; D013925:Thromboplastin / Q000502:physiology*; D014805:Vitamin B 12 / Q000097:blood; D000979:alpha-2-Antiplasmin / Q000032:analysis; D053482:beta 2-Glycoprotein I
chemical_list: D003278:Contraceptives, Oral, Hormonal; D006023:Glycoproteins; D019007:P-Selectin; D018180:Thrombomodulin; D000979:alpha-2-Antiplasmin; D053482:beta 2-Glycoprotein I; C064015:factor XIII subunit A; D005176:Factor XIII; D013925:Thromboplastin; D005492:Folic Acid; C054380:factor XIIIb; D014805:Vitamin B 12