Study Report - GWAS of hypertension in a British population (HGVST9)
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Explore Study in Browser| Identifier | HGVST9 | |||||||||||||||
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| Study name | GWAS of hypertension in a British population | |||||||||||||||
| Total p-values imported | 65 | |||||||||||||||
| Phenotype(s) tested | Hypertension |
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| Study design | Case and control | |||||||||||||||
| Genotype platforms |
Affymetrix 500K Gene Chip | |||||||||||||||
| Abstract | Summary-level data and analysis results of Hypertension (HT) imported from the Wellcome Trust Case Control Consortium project | |||||||||||||||
| Submission information |
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Author communication  |
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| Related links |
WTCCC1 |
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| Background | The Wellcome Trust Case Control Consortium (WTCCC) was formed with a view to exploring the utility, design and analyses of GWA studies. It brought together over 50 research groups from the UK that are active in researching the genetics of common human diseases, with expertise ranging from clinical, through genotyping, to informatics and statistical analysis | |||||||||||||||
| Objectives | The main experiment consisted of a GWA study of 2,000 cases and 3,000 shared controls for a complex human disease of major public health importance, Hypertension (HT). By simultaneously studying Crohn's Disease (CD) with other diseases with differing aetiologies, we hoped to develop in sights, not only into the specific genetic contributions to each of the diseases, but also into differences in allelic architecture across the diseases. A further major aim was to address important methodological issues of relevance to all GWA studies, such as quality control, design and analysis. In addition to our main association results, we address several of these issues below, including the choice of controls for genetic studies, the extent of population structure within Great Britain, sample sizes necessary to detect genetic effects of varying sizes, and improvements in genotype-calling algorithms and analytical methods. | |||||||||||||||
| Key results | For HT there were no SNPs with significance below 5x10-7 but the number and distribution of association signals in the range 10-4 to 10-7 was similar to that of the other diseases studied. The most strongly associated SNPs do not identify genes from physiological systems previously implicated by clinical or genetic studies in hypertension. The strongest signal overall is with rs2820037 on 1q43 (genotypic test, P = 7.7x10-7). | |||||||||||||||
| Conclusions | None of the variants previously associated with Hypertension (HT) showed evidence for association in our study although we note that some, such as promoter of the WNK1 (WNK lysine deficient protein kinase 1) gene, are not well tagged by the Affymetrix chip.Possible explanations include, First, HT may have fewer common risk alleles of larger effect sizes than some of the other complex phenotypes. If so, then identification of susceptibility variants for HT is likely to be reliant on the synthesis of findings from multiple large-scale studies. Second, the present study may have failed to detect genuine common susceptibility variants of large effect size because they happened to be poorly tagged by the set of SNPs genotyped in the current study. If so, further rounds of genotyping using resources that offer increased density (or complementary SNP sets), and/or improved analytical methods (for example, imputation-based) should facilitate their discovery. Third, study of HT may be more susceptible than other phenotypes to the diluting effects of misclassification bias due to the presence of hypertensive individuals within the control samples. If so, power can be improved in future studies by use of controls specifically screened to exclude individuals with elevated blood pressure. | |||||||||||||||
| Reason for study size | Not supplied | |||||||||||||||
| Study power | Not supplied | |||||||||||||||
| Sources of bias | Not supplied | |||||||||||||||
| Limitations | Not supplied | |||||||||||||||
| Acknowledgements | The principal funder of this project was the Wellcome Trust. Please see publication for the full list of acknowledgements. | |||||||||||||||
| Related citations |
The Wellcome Trust Case Control Consortium
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007 Jun 7;447(7145):661-78 |
