Replication of the Wellcome Trust genome-wide association study of essential hypertension: The Family Blood Pressure Program

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

Research output: Contribution to journalArticle

Abstract

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 500000 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 11433 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.

Original languageEnglish (US)
Pages (from-to)1507-1511
Number of pages5
JournalEuropean Journal of Human Genetics
Volume16
Issue number12
DOIs
StatePublished - 2008
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Ehret, G. B., Morrison, A. C., O'Connor, A. A., Grove, M. L., Baird, L., Schwander, K., Weder, A., Cooper, R. S., Rao, D. C., Hunt, S. C., Boerwinkle, E., & Chakravarti, A. (2008). Replication of the Wellcome Trust genome-wide association study of essential hypertension: The Family Blood Pressure Program. European Journal of Human Genetics, 16(12), 1507-1511. https://doi.org/10.1038/ejhg.2008.102