Journal
JOURNAL OF HYPERTENSION
Volume 29, Issue 1, Pages 62-69Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/HJH.0b013e3283406927
Keywords
blood pressure; genetics; hypertension; women
Categories
Funding
- National Heart, Lung, and Blood Institute [HL-043851, HL-69757]
- National Cancer Institute [CA-047988]
- Donald W. Reynolds Foundation
- Fondation Leducq
- Amgen
- National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]
- DIVISION OF EPIDEMIOLOGY AND CLINICAL APPLICATIONS [N01HC025195] Funding Source: NIH RePORTER
- NATIONAL CANCER INSTITUTE [R01CA047988] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [U01HL069757, U19HL069757, R01HL043851, ZIAHL006001] Funding Source: NIH RePORTER
Ask authors/readers for more resources
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 singlenucleotide polymorphisms ( SNPs) with genome-wide significance ( P < 5.0 X 10(-8), 'primary'), and 13 suggestive SNPs ( 5.0 x 10(-8) < P< 5.6 x 10(-5), '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 x 10(-8)). 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. J Hypertens 29:62-69 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available