| Discovery and replication of novel blood pressure genetic loci in the Women's Genome Health Study. | |
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MedLine Citation:
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PMID: 21045733 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 × 10⁻⁸, 'primary'), and 13 suggestive SNPs (5.0 × 10⁻⁸ < P < 5.6 × 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 × 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. |
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Authors:
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Jennifer E Ho; Daniel Levy; Lynda Rose; Andrew D Johnson; Paul M Ridker; Daniel I Chasman |
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Publication Detail:
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Type: Journal Article; Meta-Analysis; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Validation Studies |
Journal Detail:
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Title: Journal of hypertension Volume: 29 ISSN: 1473-5598 ISO Abbreviation: J. Hypertens. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-16 Completed Date: 2011-04-25 Revised Date: 2012-01-04 |
Medline Journal Info:
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Nlm Unique ID: 8306882 Medline TA: J Hypertens Country: England |
Other Details:
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Languages: eng Pagination: 62-9 Citation Subset: IM |
Affiliation:
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National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Blood Pressure
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genetics* Female Genome, Human* Genome-Wide Association Study Humans Polymorphism, Single Nucleotide* Women's Health* |
| Grant Support | |
ID/Acronym/Agency:
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CA-047988/CA/NCI NIH HHS; HL-043851/HL/NHLBI NIH HHS; HL-69757/HL/NHLBI NIH HHS; N01-HC-25195/HC/NHLBI NIH HHS; Z01 HL006001-01/HL/NHLBI NIH HHS; Z01 HL006001-02/HL/NHLBI NIH HHS; ZIA HL006001-03/HL/NHLBI NIH HHS; ZIA HL006001-04/HL/NHLBI NIH HHS |
| Comments/Corrections | |
Comment In:
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J Hypertens. 2011 Jan;29(1):32
[PMID:
21160361
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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