Genome-wide linkage scan in affected sibling pairs identifies novel susceptibility region for venous thromboembolism: Genetics In Familial Thrombosis study
| Autor: | V. Van Marion, R. van Minkelen, F. R. Rosendaal, M. den Heijer, Jeanine J. Houwing-Duistermaat, M. de Visser, Hans L. Vos, Rogier M. Bertina, Jeroen Eikenboom, P.E. Slagboom |
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| Přispěvatelé: | Internal medicine, ICaR - Circulation and metabolism |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Genetic Markers Male Adolescent Genotype Single-nucleotide polymorphism Thrombophilia Polymorphism Single Nucleotide Young Adult genetic linkage Risk Factors Genetic linkage Surveys and Questionnaires ABO blood group system Factor V Leiden medicine Humans SNP Genetic Predisposition to Disease cardiovascular diseases Allele Genotyping Alleles siblings thrombosis Aged Netherlands thrombophilia Aged 80 and over Genetics business.industry Venous Thromboembolism Hematology Middle Aged thromboembolism medicine.disease Case-Control Studies Female Lod Score business |
| Zdroj: | Journal of Thrombosis and Haemostasis, 11(8), 1474-1484. Wiley-Blackwell Journal of Thrombosis and Haemostasis, 11(8), 1474-1484 de Visser, M C H, van Minkelen, R, van Marion, V, den Heijer, M, Eikenboom, J, de Vos, H, Slagboom, P, Houwing-Duistermaat, J, Rosendaal, F & Bertina, R 2013, ' Genome-wide linkage scan in affected sibling pairs identifies novel susceptibility region for venous thromboembolism: Genetics In Familial Thrombosis study ', Journal of Thrombosis and Haemostasis, vol. 11, no. 8, pp. 1474-1484 . https://doi.org/10.1111/jth.12313 |
| ISSN: | 1538-7933 |
| DOI: | 10.1111/jth.12313 |
| Popis: | Summary. Background: Venous thromboembolism (VTE) is a multicausal disorder involving environmental and genetic risk factors. In many thrombophilic families the clustering of thrombotic events cannot be explained by known genetic risk factors, indicating that some remain to be discovered. Objectives: We aimed to identify novel thrombosis susceptibility alleles in a large panel of small thrombophilic families: the Genetics In Familial Thrombosis (GIFT) study. Patients/Methods: In the GIFT study, 201 families were recruited consisting of 438 siblings with an objectively confirmed VTE at a young age. Multipoint linkage analysis (402 SSR markers) and fine mapping were performed, followed by genotyping of tagging SNPs in positional candidate genes. Results: Established genetic risk factors such as factor V Leiden, ABO blood group non-O, prothrombin 20210A, fibrinogen gamma 10034T and deficiencies of antithrombin, protein C and protein S were more frequent in GIFT patients than in unselected VTE patients. Linkage supported the presence of novel thrombosis susceptibility loci on 7p21.3–22.2 (LOD score = 3.23) and Xq24–27.3 (LOD score = 1.95). Simulation analysis showed that the chr7 signal was genome-wide statistically significant (P = 0.022). Tagging SNPs (n = 157) in eight positional candidate genes (LOD drop 1.5 regions) were genotyped in GIFT patients and 332 healthy controls. Five chr7 SNPs associated with VTE. SNP THSD7A rs2074597 was responsible for part of the chr7 signal. Conclusions: The GIFT panel is rich in established genetic risk factors for VTE, but genetic factors remain unidentified in many families. Genome-wide linkage failed to identify the previously established genetic risk factors for VTE, but identified a novel VTE susceptibility locus on chr7. |
| Databáze: | OpenAIRE |
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