A study of the genetics of hypertension


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Title A study of the genetics of hypertension
Period 12 / 2000 - 12 / 2003
Status Completed
Research number OND1281829


Hypertension is a common disorder and an important cause of renal and vascular disease. It has long been recognised that genetic factors play a major role in its etiology. Pathogenesis of hypertension is complex, in that the disease is most likely the result of the interplay between multiple genes and environmental factors. The power of classical linkage analysis and affected sib-pair analysis to identify genes implicated in such a complex disorder is low and little progress has been made in unraveling the genetics of primary hypertension. Here, we propose a novel population-based method developed in the Netherlahds to localise genes that play a role in hypertension. The rationale of the method is that in a genetically isolated population the number of genes implicated in a complex disorder is strongly reduced because of genetic drift. Patients from recently isolated populations who inherited the disease from a common ancestor are likely to share considerable parts of DNA around disease gene(s). These segments can be localised in a genomic sereen with a coarse grid of markers. The study proposed here aims to localise new genes implicated in hypertension in a study of hypertensive subjects from a genetically isolated population. This study will be conducted in a genetically isolated village in the Southern part of the Netherlands (indicated as GRIP1) that has a suitable structure for this novel method. Simulation studies show that a genomic search (marker spacing: 5-10 cM) for genes implicated in hypertension can be conducted with sufficient statistical power using 75 selected patients. In regions of interest identified, more markers will be tested in order to characterise the risk haplotype. Although the isolation of the gene is outside the scope of this project, the risk of hypertension associated with the gene encaptured will be quantified using the risk haplotype(s) identified.

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D21400 Genetics
D23220 Internal medicine

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