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

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

Hum Mol Genet 2013 Apr 8;22(8):1663-78. Epub 2013 Jan 8.

Division of Cardiovascular Medicine, University of Michigan Health System, Ann Arbor, MI, USA.

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.

Download full-text PDF

Source
http://hmg.oxfordjournals.org/content/22/8/1663.full.pdf
Web Search
http://www.hmg.oxfordjournals.org/cgi/doi/10.1093/hmg/dds555
Publisher Site
http://dx.doi.org/10.1093/hmg/dds555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657476PMC
April 2013
87 Reads
50 Citations
6.393 Impact Factor

Publication Analysis

Top Keywords

european ancestry
8
identified novel
8
snps mdm4
8
sbp chromosome
8
blood pressure
8
loci associated
8
individuals european
8
associations
5
eqtl analysis
4
3p253 intron
4
chromosome 3p253
4
novel snps
4
associations snps
4
analysis associations
4
intron hrh1
4
findings expression
4
dbp chromosome1q321
4
rs2169137 dbp
4
hrh1 rs2169137
4
rs347591 sbp
4

References

(Supplied by CrossRef)
Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure
Wain et al.
Nat. Genet 2011

Similar Publications