A Genome-Wide Association Study of Hypertension and Blood Pressure in African Americans

Center for Research on Genomics and Global Health, National Human Genome Research Institute, NIH, Bethesda, MD, USA.
PLoS Genetics (Impact Factor: 7.53). 08/2009; 5(7):e1000564. DOI: 10.1371/journal.pgen.1000564
Source: PubMed


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 = 5.8 x 10(-7)) or with hypertension as a binary trait (top scoring SNP rs9791170, p = 5.1 x 10(-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.

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Available from: Adebowale Adeyemo, Oct 05, 2015
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    • "In disease state SEL1L and SELS proteins are found to be underexpressed [56] whereas PFKL and PFKP over-express [57]. In addition to the above proteins, C1S, YWHAE, CALM1, CALM2, CALM3 and MT-CO3 are responsible for obesity in turn regulating levels of insulin leading to insulin resistance in the body and thus contributing to the occurrence the disease [58] [59] [60]. The proteins PSMD1, PSMD11, PSME1 and PSMB8 form a complex in the "
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    • "We used the keywords " race " , " racial differences " , " hypertension " , and " diabetes " in various combinations to search the NIH database to find grant proposals funded between 2000–2012 containing the keywords in their project titles or abstracts. We did these analyses to determine whether NIH funded biomedical research that examined racial correlates of hypertension and diabetes, both of which are common in the African-American population (Brancati et al. 2000; Adeyemo et al. 2009). If NIH funded research on these topics, then it would indicate that there are no organizational prohibitions of funding biomedical research examining the influences of innate individual and population differences in the development and presentation of disease. "
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    • "Two variants in this gene have been identified in Pakistani families with amelogenesis imperfecta (AI), and Slc24a4 knockout mice have severe enamel defects, indicating a role for this solute carrier in amelogenesis [97]. Perhaps of most relevance to AD is the association of this gene with blood pressure in African Americans as AD may be influenced by vascular disease [98]. "
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