Venous thrombosis (VT) is a multicausal disease that is caused by the interaction of both genetic and acquired risk factors. The aim of the studies described in this thesis was to identify novel genes or genomic regions that contribute to the susceptibility of VT. We used two different approaches to achieve this goal: the hypothesis-based candidate gene approach and the discovery-based genome-wide approach. The candidate genes investigated are factor VII-activating protease, coagulation factor IX and four interleukin-1 related genes. As a second approach we used a genome-wide linkage approach to systematically scan the genome for genes or genomic regions that contribute to the susceptibility of venous thromboembolism (VTE). For this purpose we recruited a panel of affected sibling pairs with VTE at a young age (Genetics In Familial Thrombosis study, GIFT). Two novel susceptibility regions for VTE were identified. We screened eleven candidate genes, selected from both regions, to investigated whether variants of these genes could explain the observed linkage signals. Identification of the gene(s) and their functional variants, which are responsible for the linkage signals, will give better insights in the molecular genetics of familial thrombophilia and might be important for the diagnosis, treatment and prevention of VTE.UBL - phd migration 201
