A number of genome-wide genetic linkage studies of hypertension in affected relative pairs (Caulfield et al., 2003; Kardia et al., 2003; Rao et al., 2003; von Wowern et al., 2003), quantitative levels of blood pressure (de Lange et al., 2004; James et al., 2003) or other study designs have been undertaken in an attempt to localize genes with substantial effects. Candidate gene investigations comparing case/ control allele frequencies have also been widely applied in studies of hypertension.
Two features that are critical for the design of linkage studies are the diagnostic criteria used for inclusion of patients, and the sample size (number of affected sib pairs or other informative relative pairs). Statistical evaluation under simple genetic models show that adequate power to detect loci that contribute say ~5% of blood pressure variance will only be obtained in linkage studies with more than 1000 affected relative pairs selected in the upper extreme of the blood pressure distribution
(e.g. the upper 5% or even better, upper 1% of the blood pressure distribution adjusted for age and sex). Only a few linkage investigations to date could be said to approach these power requirements, notably the British Genetics of Hypertension Study (BRIGHT) (Caulfield et al., 2003) and the NIH HyperGen study (Rao et al., 2003). BRIGHT, which is the largest individual study, comprises more than 2000 affected sibpairs selected to be in the upper 10%—5% of the blood pressure distribution. Based on genome-wide linkage mapping, four regions of suggestive linkage were reported in BRIGHT, including one region with a LOD score of 3.2. Different regions with suggestive evidence of linkage to hypertension susceptibility have been observed in the HyperGen study and the other investigations cited above.
A feature in many of these genetic investigations has been the incorporation of additional traits that are related to hypertension. For example, HyperGen has included linkage studies of pulse pressure, echocardiography, heart rate, lipids, age-at-diagnosis and other phenotypes measured in the hypertensive families, but again only suggestive evidence of linkage have been reported. The analysis of blood pressure measurements as quantitative traits has revealed stronger evidence of linkage in some studies, particularly the Framingham Heart Study for which longitudinal data can be analysed (James et al., 2003; Levy et al., 2000). Some other intermediate phenotypes for blood pressure are discussed below.
The linkage results for hypertension are similar to those seen in many other multifactorial diseases. They suggest that the loci underlying susceptibility to hypertension have at best a modest effect in the populations from which these study samples have been selected. Nevertheless, it may be possible to identify some of the susceptibility genes by a combination of additional linkage and association mapping. Further mapping and additional meta-analyses involving the pooling of data from different genome screens may be helpful in confirming or identifying new linkage regions (Liu et al., 2004; Province et al., 2003).
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Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...