Discovery and replication of novel blood pressure ... [J Hypertens. 2010] - PubMed result

J Hypertens. 2010 Oct 30. [Epub ahead of print]
Discovery and replication of novel blood pressure genetic loci in the Women's Genome Health Study.

Ho JE, Levy D, Rose L, Johnson AD, Ridker PM, Chasman DI.

aNational Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA bCenter for Population Studies, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA cCenter for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, Massachusetts, USA dDonald W Reynolds Center for Cardiovascular Research, Harvard Medical School, Boston, Massachusetts, USA *Daniel Levy and Daniel I. Chasman contributed equally to the writing of this article.

Abstract

OBJECTIVES: Genome-wide association meta-analyses have recently identified multiple loci associated with blood pressure. We sought to validate previously identified blood pressure loci by replication in a single large homogeneous population-based cohort and to identify new genome-wide significant loci using both conventional and expression-guided approaches.

METHODS: We examined the associations of 18 single-nucleotide polymorphisms (SNPs) with genome-wide significance (P < 5.0 × 10, 'primary'), and 13 suggestive SNPs (5.0 × 10 < P < 5.6 × 10, 'secondary'), all from previously established genome-wide association studies, with self-reported blood pressure in 23 019 women from the Women's Genome Health Study. We then targeted for replication 12 gene expression-associated SNPs (eSNPs) that were also previously associated with blood pressure phenotypes.

RESULTS: Using these replication strategies, we found confirmatory evidence for 13/18 primary SNPs, 3/13 secondary SNPs, and 4/12 eSNPs in the Women's Genome Health Study. Meta-analysis combining the Women's Genome Health Study results with prior study results revealed one previously unrecognized blood pressure locus with genome-wide significance: a BLK-GATA4-adjacent region (P = 3.2 × 10).

CONCLUSION: In this analysis, conventional and eSNP-guided strategies were complementary and illustrate two ways for extending initial genome-wide association results for discovery of new genes involved in human disease. Using this strategy, we report a newly identified blood pressure locus, BLK-GATA4, that may further understanding of the complex genetic pathways regulating blood pressure.

PMID: 21045733 [PubMed - as supplied by publisher]
Discovery and replication of novel blood pressure ... [J Hypertens. 2010] - PubMed result