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


Show simple item record Adeyemo, Adebowale en_US Gerry, Norman en_US Chen, Guanjie en_US Herbert, Alan en_US Doumatey, Ayo en_US Huang, Hanxia en_US Zhou, Jie en_US Lashley, Kerrie en_US Chen, Yuanxiu en_US Christman, Michael en_US Rotimi, Charles en_US 2012-01-11T22:27:19Z 2012-01-11T22:27:19Z 2009-7-17 en_US
dc.identifier.citation Adeyemo, Adebowale, Norman Gerry, Guanjie Chen, Alan Herbert, Ayo Doumatey, Hanxia Huang, Jie Zhou, Kerrie Lashley, Yuanxiu Chen, Michael Christman, Charles Rotimi. "A Genome-Wide Association Study of Hypertension and Blood Pressure in African Americans" PLoS Genetics 5(7):e1000564. (2009) en_US
dc.identifier.issn 1553-7404 en_US
dc.description.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 = 5.8×10−7) or with hypertension as a binary trait (top scoring SNP rs9791170, p = 5.1×10−7). 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. Author Summary Despite intense research, the genetic risk factors for essential hypertension and blood pressure (BP) regulation have not been identified with consistency. We conducted a genome wide association scan using over 800,000 genetic markers in an African American sample of 1,017 adults in the Washington, D.C., area of the United States. We found evidence to suggest that genetic variants in several genes, including PMS1, SLC24A4, YWHA7, IPO7, and CACANA1H, are significantly associated with systolic BP levels. From our previous knowledge of human physiology, two of these genes have potential roles to play in BP regulation. The evidence for genetic variants influencing diastolic BP levels and hypertension status was weaker and inconclusive. To our knowledge, this is the first study that has used a genome-wide association approach to study hypertension and BP in an African American population, a minority group that experiences hypertension more frequently and more severely than other population groups in the United States. The findings will be useful to other researchers seeking to advance our understanding of the genetic factors that influence BP with the hope that these insights will eventually translate to new and better treatment options for hypertension in African Americans and other global populations. en_US
dc.description.sponsorship NIGMS/MBRS/SCORE Program (S06GM008016-320107, S06GM008016-380111); National Center for Research Resources (2M01RR010284); Coriell Institute for Biomedical Sciences; Intramural Research Program of the National Human Genome Research Institute; National Institutes of Health (Z01HG200362) en_US
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.rights This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. en_US
dc.title A Genome-Wide Association Study of Hypertension and Blood Pressure in African Americans en_US
dc.type article en_US
dc.identifier.doi 10.1371/journal.pgen.1000564 en_US
dc.identifier.pubmedid 19609347 en_US
dc.identifier.pmcid 2702100 en_US

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