Genetic susceptibility to thrombosis and its relationship to physiological risk factors: The GAIT study

Juan Carlos Souto, Laura Almasy, Montserrat Borrell, Francisco Blanco-Vaca, Jos� Mateo, Jos� Manuel Soria, Inma Coll, Rosa Felices, William Stone, Jordi Fontcuberta, John Blangero

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251 Scopus citations


Although there are a number of well-characterized genetic defects that lead to increased risk of thrombosis, little information is available on the relative importance of genetic factors in thrombosis risk in the general population. We performed a family-based study of the genetics of thrombosis in the Spanish population to assess the heritability of thrombosis and to identify the joint actions of genes on thrombosis risk and related quantitative hemostasis phenotypes. We examined 398 individuals in 21 extended pedigrees. Twelve pedigrees were ascertained through a proband with idiopathic thrombosis, and the remaining pedigrees were randomly ascertained. The heritability of thrombosis liability and the genetic correlations between thrombosis and each of the quantitative risk factors were estimated by means of a novel variance component method that used a multivariate threshold model. More than 60% of the variation in susceptibility to common thrombosis is attributable to genetic factors. Several quantitative risk factors exhibited significant genetic correlations with thrombosis, indicating that some of the genes that influence quantitative variation in these physiological correlates also influence the risk of thrombosis. Traits that exhibited significant genetic correlations with thrombosis included levels of several coagulation factors, factors VII, VIII, IX, XI, XII, and von Willebrand), tissue plasminogen activator, homocysteine, and the activated protein C ratio. This is the first study that quantifies the genetic component of susceptibility to common thrombosis. The high heritability of thrombosis risk and the significant genetic correlations between thrombosis and related risk factors suggest that the exploitation of correlated quantitative phenotypes will aid the search for susceptibility genes.

Original languageEnglish (US)
Pages (from-to)1452-1459
Number of pages8
JournalAmerican Journal of Human Genetics
Issue number6
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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