Loci influencing blood pressure identified using a cardiovascular gene-centric array

Ganesh S.K., Tragante V., Guo W., Guo Y., Lanktree M.B., Smith E.N., Johnson T., Castillo B.A., Barnard J., Baumert J., Chang Y.-P.C., Elbers C.C., Farrall M., Fischer M.E., Franceschini N., Gaunt T.R., Gho J.M.I.H., Gieger C., Gong Y., Isaacs A., Kleber M.E., Leach I.M., McDonough C.W., Meijs M.F., Mellander O., Molony C.M., Nolte I.M., Padmanabhan S., Price T.S., Rajagopalan R., Shaffer J., Shah S., Shen H., Soranzo N., van der Most P.J., Van Iperen E.P.A., Van Setten J.A., Vonk J.M., Zhang L., Beitelshees A.L., Berenson G.S., Bhatt D.L., Boer J.M.A., Boerwinkle E., Burkley B., Burt A., Chakravarti A., Chen W., Cooper-DeHoff R.M., Curtis S.P., Dreisbach A., Duggan D., Ehret G.B., Fabsitz R.R., Fornage M., Fox E., Furlong C.E., Gansevoort R.T., Hofker M.H., Hovingh G.K., Kirkland S.A., Kottke-Marchant K., Kutlar A., LaCroix A.Z., Langaee T.Y., Li Y.R., Lin H., Liu K., Maiwald S., Malik R., Murugesan G., Newton-Cheh C., O'Connell J.R., Onland-Moret N.C., Ouwehand W.H., Palmas W., Penninx B.W., Pepine C.J., Pettinger M., Polak J.F., Ramachandran V.S., Ranchalis J., Redline S., Ridker P.M., Rose L.M., Scharnag H., Schork N.J., Shimbo D., Shuldiner A.R., Srinivasan S.R., Stolk R.P., Taylor H.A., Thorand B., Trip M.D., van Duijn C.M., Verschuren W.M., Wijmenga C., Winkelmann B.R., Wyatt S., Young J.H., Boehm B.O., Caulfield M.J., Chasman D.I., Davidson K.W., Doevendans P.A., FitzGerald G.A., Gums J.G., Hakonarson H., Hillege H.L., Illig T., Jarvik G.P., Johnson J.A., Kastelein J.J., Koenig W., Study L.C., Marz W., Mitchell B.D., Murray S.S., Oldehinkel A.J., Rader D.J., Reilly M.P., Reiner A.P., Schadt E.E., Silverstein R.L., Snieder H., Stanton A.V., Uitterlinden A.G., van der Harst P., van der Schouw Y.T., Samani N.J., Johnson A.D., Munroe P.B., de Bakker P.I.W., Zhu X., Levy D., Keating B.J. and Asselbergs F.W. (2013) Loci influencing blood pressure identified using a cardiovascular gene-centric array. Human Molecular Genetics, 22 8: 1663-1678. doi:10.1093/hmg/dds555

Author Ganesh S.K.
Tragante V.
Guo W.
Guo Y.
Lanktree M.B.
Smith E.N.
Johnson T.
Castillo B.A.
Barnard J.
Baumert J.
Chang Y.-P.C.
Elbers C.C.
Farrall M.
Fischer M.E.
Franceschini N.
Gaunt T.R.
Gho J.M.I.H.
Gieger C.
Gong Y.
Isaacs A.
Kleber M.E.
Leach I.M.
McDonough C.W.
Meijs M.F.
Mellander O.
Molony C.M.
Nolte I.M.
Padmanabhan S.
Price T.S.
Rajagopalan R.
Shaffer J.
Shah S.
Shen H.
Soranzo N.
van der Most P.J.
Van Iperen E.P.A.
Van Setten J.A.
Vonk J.M.
Zhang L.
Beitelshees A.L.
Berenson G.S.
Bhatt D.L.
Boer J.M.A.
Boerwinkle E.
Burkley B.
Burt A.
Chakravarti A.
Chen W.
Cooper-DeHoff R.M.
Curtis S.P.
Dreisbach A.
Duggan D.
Ehret G.B.
Fabsitz R.R.
Fornage M.
Fox E.
Furlong C.E.
Gansevoort R.T.
Hofker M.H.
Hovingh G.K.
Kirkland S.A.
Kottke-Marchant K.
Kutlar A.
LaCroix A.Z.
Langaee T.Y.
Li Y.R.
Lin H.
Liu K.
Maiwald S.
Malik R.
Murugesan G.
Newton-Cheh C.
O'Connell J.R.
Onland-Moret N.C.
Ouwehand W.H.
Palmas W.
Penninx B.W.
Pepine C.J.
Pettinger M.
Polak J.F.
Ramachandran V.S.
Ranchalis J.
Redline S.
Ridker P.M.
Rose L.M.
Scharnag H.
Schork N.J.
Shimbo D.
Shuldiner A.R.
Srinivasan S.R.
Stolk R.P.
Taylor H.A.
Thorand B.
Trip M.D.
van Duijn C.M.
Verschuren W.M.
Wijmenga C.
Winkelmann B.R.
Wyatt S.
Young J.H.
Boehm B.O.
Caulfield M.J.
Chasman D.I.
Davidson K.W.
Doevendans P.A.
FitzGerald G.A.
Gums J.G.
Hakonarson H.
Hillege H.L.
Illig T.
Jarvik G.P.
Johnson J.A.
Kastelein J.J.
Koenig W.
Study L.C.
Marz W.
Mitchell B.D.
Murray S.S.
Oldehinkel A.J.
Rader D.J.
Reilly M.P.
Reiner A.P.
Schadt E.E.
Silverstein R.L.
Snieder H.
Stanton A.V.
Uitterlinden A.G.
van der Harst P.
van der Schouw Y.T.
Samani N.J.
Johnson A.D.
Munroe P.B.
de Bakker P.I.W.
Zhu X.
Levy D.
Keating B.J.
Asselbergs F.W.
Title Loci influencing blood pressure identified using a cardiovascular gene-centric array
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
Publication date 2013-04-01
Year available 2013
Sub-type Article (original research)
DOI 10.1093/hmg/dds555
Open Access Status DOI
Volume 22
Issue 8
Start page 1663
End page 1678
Total pages 16
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Subject 1311 Genetics
2716 Genetics (clinical)
1312 Molecular Biology
Formatted abstract
Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped ~50 000 single-nucleotide polymorphisms (SNPs) that capture variation in ~2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P < 2.4 × 10-6). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.
Keyword Biochemistry & Molecular Biology
Genetics & Heredity
Biochemistry & Molecular Biology
Genetics & Heredity
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID N01-HC-65226
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
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