Blood pressure loci identified with a gene-centric array.

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.; Sever, P.; Shields, D.C.; Thom, S.; Wannamethee, S.G.; Whincup, P.H.; Brown, M.J.; Connell, J.M.; Dobson, R.J.; Howard, P.J.; Mein, C.A.; Onipinla, A.; Shaw-Hawkins, S.; Zhang, Y.; Davey Smith, G.; Day, I.N.; Lawlor, D.A.; Goodall, A.H.; Fowkes, F.G.; Abecasis, G.R.; Elliott, P.; Gateva, V.; Braund, P.S.; Burton, P.R.; Nelson, C.P.; Tobin, M.D.; van der Harst, P.; Glorioso, N.; Neuvrith, H.; Salvi, E.; Staessen, J.A.; Stucchi, A.; Devos, N.; Jeunemaitre, X.; Plouin, P.F.; Tichet, J.; Juhanson, P.; Org, E.; Putku, M.; Sõber, S.; Veldre, G.; Viigimaa, M.; Levinsson, A.; Rosengren, A.; Thelle, D.S.; Hastie, C.E.; Hedner, T.; Lee, W.K.; Melander, O.; Wahlstrand, B.; Hardy, R.; Wong, A.; Cooper, J.A.; Palmen, J.; Chen, L.; Stewart, A.F.; Wells, G.A.; Westra, H.J.; Wolfs, M.G.; Clarke, R.; Franzosi, M.G.; Goel, A.; Hamsten, A.; Lathrop, M.; Peden, J.F.; Seedorf, U.; Watkins, H.; Ouwehand, W.H.; Sambrook, J.; Stephens, J.; Casas, J.P.; Drenos, F.; Holmes, M.V.; Kivimaki, M.; Shah, S.; Shah, T.; Talmud, P.J.; Whittaker, J.; Wallace, C.; Delles, C.; Laan, M.; Kuh, D.; Humphries, S.E.; Nyberg, F.; Cusi, D.; Roberts, R.; Newton-Cheh, C.; Franke, L.; Stanton, A.V.; Dominiczak, A.F.; Farrall, M.; Hingorani, A.D.; Samani, N.J.; Caulfield, M.J.; Munroe, P.B.

doi:10.1016/j.ajhg.2011.10.013

Blood pressure loci identified with a gene-centric array.

Details

Download: 1-s2.0-S0002929711004472-main.pdf (1016.90 [Ko])
State: Public
Version: Final published version

Serval ID

serval:BIB_4869D08B96FA

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

Blood pressure loci identified with a gene-centric array.

Journal

American journal of human genetics

Author(s)

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., Sever P., Shields D.C., Thom S., Wannamethee S.G., Whincup P.H., Brown M.J., Connell J.M., Dobson R.J., Howard P.J., Mein C.A., Onipinla A., Shaw-Hawkins S., Zhang Y., Davey Smith G., Day I.N., Lawlor D.A., Goodall A.H., Fowkes F.G., Abecasis G.R., Elliott P., Gateva V., Braund P.S., Burton P.R., Nelson C.P., Tobin M.D., van der Harst P., Glorioso N., Neuvrith H., Salvi E., Staessen J.A., Stucchi A., Devos N., Jeunemaitre X., Plouin P.F., Tichet J., Juhanson P., Org E., Putku M., Sõber S., Veldre G., Viigimaa M., Levinsson A., Rosengren A., Thelle D.S., Hastie C.E., Hedner T., Lee W.K., Melander O., Wahlstrand B., Hardy R., Wong A., Cooper J.A., Palmen J., Chen L., Stewart A.F., Wells G.A., Westra H.J., Wolfs M.G., Clarke R., Franzosi M.G., Goel A., Hamsten A., Lathrop M., Peden J.F., Seedorf U., Watkins H., Ouwehand W.H., Sambrook J., Stephens J., Casas J.P., Drenos F., Holmes M.V., Kivimaki M., Shah S., Shah T., Talmud P.J., Whittaker J., Wallace C., Delles C., Laan M., Kuh D., Humphries S.E., Nyberg F., Cusi D., Roberts R., Newton-Cheh C., Franke L., Stanton A.V., Dominiczak A.F., Farrall M., Hingorani A.D., Samani N.J., Caulfield M.J., Munroe P.B.

Working group(s)

Cardiogenics Consortium, Global BPgen Consortium

Contributor(s)

Newton-Cheh C., Johnson T., Gateva V., Tobin M.D., Bochud M., Coin L., Najjar S.S., Hua J., Heath S.C., Eyheramendy S., Papadakis K., Voight B.F., Scott L.J., Zhang F., Farrall M., Tanaka T., Wallace C., Chambers J.C., Khaw K.T., Nilsson P., van der Harst P., Polidoro S., Grobbee D.E., Onland-Moret N.C., Bots M.L., Wain L.V., Elliott K.S., Teumer A., Luan J., Lucas G., Kuusisto J., Burton P.R., Hadley D., McArdle W.L., Wellcome Trust Case Control Consortium X, Brown M., Dominiczak A., Newhouse S.J., Samani N.J., Webster J., Zeggini E., Beckmann J.S., Bergmann S., Lim N., Song K., Vollenweider P., Waeber G., Waterworth D.M., Yuan X., Groop L., Orho M., Allione A., Di Gregorio A., Guarrera S., Panico S., Ricceri F., Romanazzi V., Sacerdote C., Vineis P., Barroso I., Sandhu M.S., Luben R.N., Crawford G.J., Jousilahti P., Perola M., Boehnke M., Bonnycastle L.L., Collins F.S., Jackson A.U., Mohlke K.L., Stringham H.M., Valle T.T., Willer C.J., Bergman R.N., Morken M.A., Döring A., Gieger C., Illig T., Meitinger T., Org E., Pfeufer A., Wichmann H.E., Kathiresan S., Marrugat J., O'Donnell C.J., Schwartz S.M., Siscovick D.S., Subirana I., Freimer N.B., Hartikainen A.L., McCarthy M.I., OReilly P.F., Peltonen L., Pouta A., de Jong P.E., Snieder H., van Gilst W.H., Clarke R., Goel A., Hamsten A., Peden J.F., Seedorf U., Syv C., Tognoni G., Lakatta E.G., Sanna S., Scheet P., Schlessinger D., Scuteri A., Dörr M., Ernst F., Felix S.B., Homuth G., Lorbeer R., Reffelmann T., Rettig R., Völker U., Galan P., Gut I.G., Hercberg S., Lathrop G.M., Zeleneka D., Deloukas P., Soranzo N., Williams F.M., Zhai G., Salomaa V., Laakso M., Elosua R., Forouhi N.G., Völzke H., Uiterwaal C.S., van der Schouw Y.T., Numans M.E., Matullo G., Navis G., Berglund G., Bingham S.A., Kooner J.S., Paterson A.D., Connell J.M., Bandinelli S., Ferrucci L., Watkins H., Spector T.D., Tuomilehto J., Altshuler D., Strachan D.P., Laan M., Meneton P., Wareham N.J., Uda M., Jarvelin M.R., Mooser V., Melander O., Loos R.J., Elliott P., Abecasis G.R., Caulfield M., Munroe P.B., Attwood T., Belz S., Braund P., Brocheton J., Cambien F., Cooper J., Crisp-Hihn A., Diemert P., Deloukas P., Eardman J., Foad N., Godefroy T., Goodall A.H., Gracey J., Gray E., Gwilliams R., Heimer S., Hengstenberg C., Jolley J., Krishnan U., Lloyd-Jones H., Liljedahl U., Lugauer I., Lundmark P., Maouche S., Moore J.S., Montalescot G., Muir D., Murray E., Nelson C.P., Neudert J., Niblett D., O'Leary K., Ouwehand W.H., Pollard H., Proust C., Rankin A., Rendon A., Rice C.M., Sager H.B., Samani N.J., Sambrook J., Schmitz G., Scholz M., Schroeder L., Schunkert H., Stephens J., Syvannen A.C., Tennstedt S., Wallace C.

ISSN

1537-6605 (Electronic)

ISSN-L

0002-9297

Publication state

Published

Issued date

09/12/2011

Peer-reviewed

Oui

Volume

Number

Pages

688-700

Language

english

Notes

Publication types: Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish

Abstract

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 × 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 × 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.

Keywords

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

URN

urn:nbn:ch:serval-BIB_4869D08B96FA5

OAI-PMH

oai:serval.unil.ch:BIB_4869D08B96FA

DOI

10.1016/j.ajhg.2011.10.013

Pubmed

22100073

Open Access

Yes

Create date

02/10/2014 13:34