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Study Report - GWAS of hypertension and blood pressure in African Americans (HGVST321)| HGVbaseG2P identifier | HGVST321 | |||||||||||||||
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| Study name | GWAS of hypertension and blood pressure in African Americans | |||||||||||||||
| Phenotype(s) tested | Systolic blood pressure Hypertension Diastolic blood pressure |
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| Study design | Case and control with replication | |||||||||||||||
| Genotype Platforms |
Affymetrix 6.0 GeneChip a Affymetrix 500 K GeneChip array Affymetrix Genome-Wide Human SNP Array 6.0 | |||||||||||||||
| Abstract | The evidence for the existence of genetic susceptibility variants for the common form of hypertension (essential hypertension) remains weak and inconsistent. We sought genetic variants underlying blood pressure (BP) by conducting a genome-wide association study (GWAS) among African Americans, a population group in the United States that is disproportionately affected by hypertension and associated complications, including stroke and kidney diseases. Using a dense panel of over 800,000 SNPs in a discovery sample of 1,017 African Americans from the Washington, D.C., metropolitan region, we identified multiple SNPs reaching genome-wide significance for systolic BP in or near the genes: PMS1, SLC24A4, YWHA7, IPO7, and CACANA1H. Two of these genes, SLC24A4 (a sodium/potassium/calcium exchanger) and CACNA1H (a voltage-dependent calcium channel), are potential candidate genes for BP regulation and the latter is a drug target for a class of calcium channel blockers. No variant reached genome wide significance for association with diastolic BP (top scoring SNP rs1867226, p = 5.8x10(-7)) or with hypertension as a binary trait (top scoring SNP rs9791170, p = 5.1x10(-7)). We replicated some of the significant SNPs in a sample of West Africans. Pathway analysis revealed that genes harboring top-scoring variants cluster in pathways and networks of biologic relevance to hypertension and BP regulation. This is the first GWAS for hypertension and BP in an African American population. The findings suggests that, in addition to or in lieu of relying solely on replicated variants of moderate-to-large effect reaching genome-wide significance, pathway and network approaches may be useful in identifying and prioritizing candidate genes/loci for further experiments. | |||||||||||||||
| Submission information |
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| Cross-references |
PLoS Genet 5(7): e1000564 |
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| Background | Not supplied | |||||||||||||||
| Objectives | Not supplied | |||||||||||||||
| Key results | Multiple SNPs were identified reaching genome-wide significance for systolic BP in or near the genes: PMS1, SLC24A4, YWHA7, IPO7, and CACANA1H. Two of these genes, SLC24A4 (a sodium/potassium/calcium exchanger) and CACNA1H (a voltage-dependent calcium channel), are potential candidate genes for BP regulation and the latter is a drug target for a class of calcium channel blockers. No variant reached genome wide significance for association with diastolic BP (top scoring SNP rs1867226, p = 5.8x10(-7)) or with hypertension as a binary trait (top scoring SNP rs9791170, p = 5.1x10(-7)). | |||||||||||||||
| Conclusions | Not supplied | |||||||||||||||
| Reason for study size | Not supplied | |||||||||||||||
| Study power | Not supplied | |||||||||||||||
| Sources of bias | Not supplied | |||||||||||||||
| Limitations | Not supplied | |||||||||||||||
| Acknowledgements | Not supplied | |||||||||||||||
| Other citations |
Adeyemo A, Gerry N, Chen G et al.
A genome-wide association study of hypertension and blood pressure in African Americans. PLoS Genetics 2009 Jul;5(7):e1000564 |
