Loci influencing blood pressure identified using a cardiovascular gene-centric array by Ganesh Santhi K, Tragante Vinicius, Guo Wei, Guo Yiran, Lanktree Matthew B, Smith Erin N, Johnson Toby, Castillo Berta Almoguera, Barnard John, Baumert Jens, Chang Yen-Pei Christy, Elbers Clara C, Farrall Martin, Fischer Mary E, Franceschini Nora, Gaunt Tom R, Gho Johannes M I H, Gieger Christian, Gong Yan, Isaacs Aaron, Kleber Marcus E, Leach Irene Mateo, McDonough Caitrin W, Meijs Matthijs F L, Mellander Olle, Molony Cliona M, Nolte Ilja M, Padmanabhan Sandosh, Price Tom S, Rajagopalan Ramakrishnan, Shaffer Jonathan, Shah Sonia, Shen Haiqing, Soranzo Nicole, van der Most Peter J, Van Iperen Erik P A, van Setten Jessica, Vonk Judith M, Zhang Li, Beitelshees Amber L, Berenson Gerald S, Bhatt Deepak L, Boer Jolanda M A, Boerwinkle Eric, Burkley Ben, Burt Amber, Chakravarti Aravinda, Chen Wei, Cooper-Dehoff Rhonda M, Curtis Sean P, Dreisbach Albert, Duggan David, Ehret Georg B, Fabsitz Richard R, Fornage Myriam, Fox Ervin, Furlong Clement E, Gansevoort Ron T, Hofker Marten H, Hovingh G Kees, Kirkland Susan A, Kottke-Marchant Kandice, Kutlar Abdullah, Lacroix Andrea Z, Langaee Taimour Y, Li Yun R, Lin Honghuang, Liu Kiang, Maiwald Steffi, Malik Rainer, METASTROKE, Murugesan Gurunathan, Newton-Cheh Christopher, O'Connell Jeffery R, Onland-Moret N Charlotte, Ouwehand Willem H, Palmas Walter, Penninx Brenda W, Pepine Carl J, Pettinger Mary, Polak Joseph F, Ramachandran Vasan S, Ranchalis Jane, Redline Susan, Ridker Paul M, Rose Lynda M, Scharnag Hubert, Schork Nicholas J, Shimbo Daichi, Shuldiner Alan R, Srinivasan Sathanur R, Stolk Ronald P, Taylor Herman A, Thorand Barbara, Trip Mieke D, van Duijn Cornelia M, Verschuren W Monique, Wijmenga Cisca, Winkelmann Bernhard R, Wyatt Sharon, Young J Hunter, Boehm Bernhard O, Caulfield Mark J, Chasman Daniel I, Davidson Karina W, Doevendans Pieter A, Fitzgerald Garret A, Gums John G, Hakonarson Hakon, Hillege Hans L, Illig Thomas, Jarvik Gail P, Johnson Julie A, Kastelein John J P, Koenig Wolfgang, LifeLines Cohort Study, März Winfried, Mitchell Braxton D, Murray Sarah S, Oldehinkel Albertine J, Rader Daniel J, Reilly Muredach P, Reiner Alex P, Schadt Eric E, Silverstein Roy L, Snieder Harold, Stanton Alice V, Uitterlinden André G, van der Harst Pim, van der Schouw Yvonne T, Samani Nilesh J, Johnson Andrew D, Munroe Patricia B, de Bakker Paul I W, Zhu Xiaofeng, Levy Daniel, Keating Brendan J, Asselbergs Folkert W in Human molecular genetics (2013). PubMed

Abstract

Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease. 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 ∼2,100 candidate genes for cardiovascular phenotypes in 61,619 individuals of European ancestry from cohort studies in the US 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 ten 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 value<2.4 x 10(-6)). We then replicated these associations in an independent set of 65,886 individuals of European ancestry. Findings from eQTL analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease, left ventricular hypertrophy, 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.

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