Blood pressure loci identified with a gene-centric array
Φόρτωση...
Ημερομηνία
Συγγραφείς
Johnson, T.
Gaunt, T. R.
Newhouse, S. J.
Padmanabhan, S.
Tomaszewski, M.
Kumari, M.
Morris, R. W.
Tzoulaki, I.
O'Brien, E. T.
Poulter, N. R.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Am J Hum Genet
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 x 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56 x 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.
Περιγραφή
Λέξεις-κλειδιά
Adult, Aged, Blood Pressure/genetics, Case-Control Studies, Female, Gene Expression Profiling, Gene Frequency, *Genetic Loci, Genome-Wide Association Study, Haplotypes, Humans, Hypertension/*genetics, Linkage Disequilibrium, Male, Methylenetetrahydrofolate Reductase (NADPH2)/genetics, Middle Aged, *Oligonucleotide Array Sequence Analysis, Plasma Membrane Calcium-Transporting ATPases/genetics, Polymorphism, Single Nucleotide, Receptors, Atrial Natriuretic Factor/genetics, Sequence Analysis, DNA
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/22100073
http://ac.els-cdn.com/S0002929711004472/1-s2.0-S0002929711004472-main.pdf?_tid=e3ca00761826390b2f6d2a2d345293e2&acdnat=1333123367_3bf77ea66b7a6581b942caa593d5e679
http://ac.els-cdn.com/S0002929711004472/1-s2.0-S0002929711004472-main.pdf?_tid=e3ca00761826390b2f6d2a2d345293e2&acdnat=1333123367_3bf77ea66b7a6581b942caa593d5e679
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής