Linkage of Essential Hypertension to Chromosome 18q

Kristjánsson, Kristleifur; Manolescu, Andrei; Kristinsson, A; Harðarson, Þórður; Knudsen, H; Ingason, Sigurdur; Þorleifsson, Guðmar; Frigge, Michael L.; Kong, Augustine; Gulcher, Jeffrey R.; Stefánsson, Kāri

doi:10.1161/01.hyp.0000018580.24644.18

Cited by 80 publications

(58 citation statements)

References 30 publications

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“…Multiple linkage analyses have provided statistical evidence that one or more genes on chromosome 2 between 40 and 140 cM from the tip of the p-arm influence blood pressure and hypertension status. [2][3][4][5][6][7][8] Broad linkage peaks shifted across the chromosome and the fact that every study sample does not reveal a noticeable peak in the same region are consistent with the expectation that multiple genes, each with a small effect, influence blood pressure and contribute to hypertension. The present study reports the results of a study to follow-up evidence of significant linkage on chromosome 2 to identify genes that may influence hypertension status and/or blood pressure level.…”

supporting

confidence: 76%

Positional Identification of Hypertension Susceptibility Genes on Chromosome 2

et al. 2004

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Abstract-Chromosome 2 has been consistently identified as a genomic region with genetic linkage evidence suggesting that one or more loci contributes to blood pressure and hypertension status. As with all complex disease traits, following-up linkage evidence to identify the underlying susceptibility gene(s) is an arduous yet biologically and clinically important task. Using combined positional candidate gene methods, the Family Blood Pressure Program (FBPP) has concentrated efforts in narrowing a large region of chromosome 2, demonstrating evidence for linkage in several populations, and identifying underlying candidate hypertension susceptibility gene(s). Initial informatics efforts identified the boundaries of the region and the known genes within it. A total of 82 polymorphic sites in 8 genes were genotyped in a large hypothesis-generating sample consisting of 1640 African Americans, 1339 whites, and 1616 Mexican Americans. After resampling-based false discovery adjustment, SLC4A5, a sodium bicarbonate transporter, was identified as a primary candidate gene for hypertension. Polymorphisms in SLC4A5 were subsequently genotyped and analyzed for validation in two other subcomponents of the FBPP, each contributing African Americans (Nϭ461; Nϭ778) and whites (Nϭ550; Nϭ967). Again, single nucleotide polymorphisms within this gene were significantly associated with blood pressure levels and hypertension status. Although not identifying a single causal gene variant that is significantly associated with blood pressure levels and hypertension status across all samples, the results further implicate SLC4A5 as a candidate hypertension susceptibility gene. Moreover, the present study validates previous evidence for one or more genes on chromosome 2 that influence hypertension-related phenotypes in the population-at-large.

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supporting

confidence: 76%

Positional Identification of Hypertension Susceptibility Genes on Chromosome 2

et al. 2004

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“…In the past few years it became feasible to genotype cheaply large pedigrees with much greater numbers of microsatellites than were previously used for genome scans, and statistical programs that are now available permit efficient computation of linkage even in complex pedigrees 28,29 . These advances allowed a substantial increase in the scale of pedigree-based linkage studies 2,4,[30][31][32][33][34][35][36][37][38] . Inadequate technology and statistical methodology have similarly hindered implementation of alternatives to pedigreebased mapping.…”

Section: Appropriate Technology and Statistics For Each Approachmentioning

confidence: 99%

The use of pedigree, sib-pair and association studies of common diseases for genetic mapping and epidemiology

2004

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Efforts to identify gene variants associated with susceptibility to common diseases use three approaches: pedigree and affected sib-pair linkage studies and association studies of population samples. The different aims of these study designs reflect their derivation from biological versus epidemiological traditions. Similar principles regarding determination of the evidence levels required to consider the results statistically significant apply to both linkage and association studies, however. Such determination requires explicit attention to the prior probability of particular findings, as well as appropriate correction for multiple comparisons. For most common diseases, increasing the sample size in a study is a crucial step in achieving statistically significant genetic mapping results. Recent studies suggest that the technology and statistical methodology will soon be available to make wellpowered studies feasible using any of these approaches.

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“…It is of note that, to our knowledge, this is the first linkage study in essential polygenic hypertension performed in Spain, and the observed results are in agreement with a recent genome-wide scan in 120 Icelandic families with EH, which showed significant linkage to 18q with no suggestive linkage to other regions. 5 Moreover, a recent study performed in Australian hypertensive sibling pairs focused specifically on chromosome 18 13 and, whereas multipoint linkage analysis produced no relevant peaks, significant single-point linkage results were found with 2 markers located on 18p and 18q. The 18p marker (D18S59), however, has also been analyzed in the present study and has shown no linkage to EH by sibling-pair analysis.…”

Section: Discussionmentioning

confidence: 99%

“…The selection of chromosomes 17 and 18 was based on evidences from genome-wide studies, 5,6 linkage analysis, and the comparative genomics strategy, 5,6,10 -13 whereas focus on chromosome 9 derived from comparative genomics. 9 …”

mentioning

confidence: 99%

Implication of Chromosome 18 in Hypertension by Sibling Pair and Association Analyses

et al. 2006

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Abstract-This study aims to test the implication of regions on chromosomes 9, 17, and 18 in essential hypertension (EH) by combining sibling-pair linkage analysis and case-control association studies. The selection of these chromosomal regions is based on previous evidence of their implication in EH or in related phenotypes by comparative genomics in several rat models and from genome-wide linkage studies in humans. For the affected sibling-pair linkage analysis, 27 microsatellite markers were genotyped in 56 pedigrees from Spain with hypertensive sibling pairs. Linkage analysis showed significant excess allele sharing at the D18S474 marker on 18q21.

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Linkage of Essential Hypertension to Chromosome 18q

Cited by 80 publications

References 30 publications

Positional Identification of Hypertension Susceptibility Genes on Chromosome 2

Positional Identification of Hypertension Susceptibility Genes on Chromosome 2

The use of pedigree, sib-pair and association studies of common diseases for genetic mapping and epidemiology

Implication of Chromosome 18 in Hypertension by Sibling Pair and Association Analyses

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