| Replication of the Wellcome Trust genome-wide association study of essential hypertension: the Family Blood Pressure Program. | |
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MedLine Citation:
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PMID: 18523456 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Essential hypertension is a principal cardiovascular risk factor whose origin remains unknown. Classical genetic studies have shown that blood pressure is at least partially heritable, opening a window to understanding the pathophysiology of essential hypertension in the human using modern genetic tools. The Wellcome Trust Case Control Consortium has recently published the results of screening the genomes of 2000 essential hypertension cases and 3000 controls using 500 000 genome-wide single nucleotide polymorphisms (SNPs). None of the variants proved to be genome-wide significant after correction for multiple tests but the most significantly associated SNPs (P<10(-5)) constitute a priority list that warrant follow-up in other studies. We describe here replication studies of the top six SNPs in subjects from the US National Heart, Lung, and Blood Institute funded Family Blood Pressure Program comprising 11 433 individuals recruited by hypertensive families. The results suggest that only one of the six SNPs might be associated with essential hypertension in Americans of European origin. This SNP shows a significant but opposite effect in Americans of Hispanic origin and no association in African Americans. The significance of the opposing effect estimates is unclear. No replication could be shown for hypertension status, but there are differences in study design. This attempted replication highlights that essential hypertension studies will require more comprehensive and larger genetic screens. |
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Authors:
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Georg B Ehret; Alanna C Morrison; Ashley A O'Connor; Megan L Grove; Lisa Baird; Karen Schwander; Alan Weder; Richard S Cooper; D C Rao; Steven C Hunt; Eric Boerwinkle; Aravinda Chakravarti |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Validation Studies Date: 2008-06-04 |
Journal Detail:
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Title: European journal of human genetics : EJHG Volume: 16 ISSN: 1018-4813 ISO Abbreviation: Eur. J. Hum. Genet. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-11-21 Completed Date: 2009-01-07 Revised Date: 2011-08-09 |
Medline Journal Info:
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Nlm Unique ID: 9302235 Medline TA: Eur J Hum Genet Country: England |
Other Details:
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Languages: eng Pagination: 1507-11 Citation Subset: IM |
Affiliation:
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McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Aged, 80 and over Blood Pressure / genetics*, physiology Blood Pressure Determination Child Family* Family Health Female Genome-Wide Association Study* Humans Hypertension / genetics*, physiopathology Male Middle Aged Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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R37 HL051021-10/HL/NHLBI NIH HHS; R37 HL051021-11/HL/NHLBI NIH HHS; R37 HL051021-12/HL/NHLBI NIH HHS; R37 HL051021-13/HL/NHLBI NIH HHS; R37 HL051021-14/HL/NHLBI NIH HHS; R37 HL051021-15/HL/NHLBI NIH HHS; U01 HL054512-12/HL/NHLBI NIH HHS |
| Comments/Corrections | |
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