Discovery and replication of novel blood pressure genetic loci in the Women's Genome Health Study
Year: 2010
Type: article
Study design: Observational Study
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 × 10⁻⁸, '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.
Source: Journal of Hypertension
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: G1528515809, G229684361, G250621538, Pharmacogenomics and Risk of Cardiovascular Disease, Framingham Project/Levy, Pharmacogenomics and Risk of Cardiovascular Disease, G5164707915, G552178769, G558986044, The Framingham Heart Study, TRIAL OF ASPIRIN AND VITAMIN E IN WOMEN, Women's Health Study: Continued Follow-up, Framingham Project/Levy
OpenAlex ID: W2062856194