Genome-wide mapping of human loci for essential hypertension

Caulfield, Mark; Munroe, Patricia B.; Pembroke, J; Samani, Nilesh J.; Dominiczak, Anna F.; Brown, Matthew A.; Benjamin, Nigel; Webster, J; Ratcliffe, Peter J.; O'Shea, S; Papp, Jeanette C.; Taylor, Eugene; Dobson, Richard; Knight, Jo; Newhouse, Stephen; Hooper, John W.; Lee, Wai Kwong; Brain, Nick J.R.; Clayton, David; Lathrop, G.M.; Farrall, Martin; Connell, John

doi:10.1016/s0140-6736(03)13722-1

Cited by 236 publications

(154 citation statements)

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“…Again, the results published so far are disappointing, with either no linkage or comparably weak linkages, e.g. to chromosomes 1, 2, 5, 6, 9 or 17, which do not overlap between different trials (Hsueh et al 2000;Levy et al 2000;Thiel et al 2003;Caulfield et al 2003;Wallace et al 2006). Candidate gene approaches revealed a wealth of interesting and not so interesting associations, but also failed to uncover relevant hypertension candidate genes so far.…”

Section: Conclusion and Future Developmentsmentioning

confidence: 99%

Genetics of arterial hypertension and hypotension

Rosskopf

Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

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Human hypertension affects affects more than 20% of the adult population in industrialized countries, and it is implicated in millions of deaths worldwide each year from stroke, heart failure and ischemic heart disease. Available evidence suggests a major genetic impact on blood pressure regulation. Studies in monogenic hypertension revealed that renal salt and volume regulation systems are predominantly involved in the genesis of these disorders. Mutations here affect the synthesis of mineralocorticoids, the function of the mineralocorticoid receptor, epithelial sodium channels and their regulation by a new class of kinases, termed WNK kinases. It has been learned from monogenic hypotension that almost all ion transporters involved in the renal uptake of Na + have a major impact on blood pressure regulation. For essential hypertension as a complex disease, many candidate genes have been analysed. These include components of the reninangiotensin-aldosterone system, adducin, β-adrenoceptors, G protein subunits, regulators of G protein signalling (RGS) proteins, Rho kinases and G protein receptor kinases. At present, the individual impact of common polymorphisms in these genes on the observed blood pressure variation, on risk for stroke and as predictors of antihypertensive responses remains small and clinically irrelevant. Nevertheless, these studies have greatly augmented our knowledge on the regulation of renal functions, cellular signal transduction and the integration of both. Together, this provides the basis for the identification of novel drug targets and, hopefully, innovative antihypertensive drugs.

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Section: Conclusion and Future Developmentsmentioning

confidence: 99%

Genetics of arterial hypertension and hypotension

Rosskopf

Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

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“…4 Interpreting GWAS results that do not result in significant associations of genetic variants with 5 disease is challenging. For example, the lack of significant associations of SNPs with 6 hypertension in the WTCCC and the British Genetics of Hypertension (BRIGHT) study [59,12] 7 [5] triggered discussions about genetics of cardiovascular diseases. However, a negative GWAS 8…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, the WTCCC 22 [5] and BRIGHT study [12] benefit by selecting cases at the top end of the blood pressure 23 distribution in a given population, since selecting extreme phenotypes increases the chance of 24 finding a genetic determinant. In our opinion, selecting extreme phenotypes, however, should 25 also be done for control subjects.…”

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confidence: 99%

“…It is now common practice that patient and control 22 cohorts are "reshuffled" and subject to more than one study. For example, the cases in the 23 WTCCC [5] derive from existing cohorts and have been analysed using different genotyping 24 technology and/or different control subjects in the past [12,50]. While the detailed statistical 25 implications of this practice are beyond the scope of this review, the amount of available 1 genotypic and phenotypic data in publicly accessible databases constitutes an enormously rich 2 resource of data.…”

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confidence: 99%

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The genetics of cardiovascular disease

Delles¹,

McBride²,

Padmanabhan³

et al. 2008

Trends in Endocrinology & Metabolism

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“…a few genes may be involved in determination of the trait) possibly superimposed on more minor genetic effects, and that several genes may be tractable to a positional cloning strategy. 29 Other researchers have demonstrated many further genetic associations but consensus is lacking. [30][31][32][33][34][35][36][37][38][39] Clearly, the availability of data from diverse populations, including Chinese, 31 Hispanics 32,33 and African-Americans 34 cohorts, is encouraging, gene variants may influence target organ damage 35 in hypertension and blood pressure variation, 36 but again, more data from diverse populations are needed.…”

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confidence: 99%