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Meta-Analysis
. 2013 Apr 15;22(8):1663-78.
doi: 10.1093/hmg/dds555. Epub 2013 Jan 8.

Loci Influencing Blood Pressure Identified Using a Cardiovascular Gene-Centric Array

Santhi K Ganesh  1 Vinicius TraganteWei GuoYiran GuoMatthew B LanktreeErin N SmithToby JohnsonBerta Almoguera CastilloJohn BarnardJens BaumertYen-Pei Christy ChangClara C ElbersMartin FarrallMary E FischerNora FranceschiniTom R GauntJohannes M I H GhoChristian GiegerYan GongAaron IsaacsMarcus E KleberIrene Mateo LeachCaitrin W McDonoughMatthijs F L MeijsOlle MellanderCliona M MolonyIlja M NolteSandosh PadmanabhanTom S PriceRamakrishnan RajagopalanJonathan ShafferSonia ShahHaiqing ShenNicole SoranzoPeter J van der MostErik P A Van IperenJessica Van SettenJudith M VonkLi ZhangAmber L BeitelsheesGerald S BerensonDeepak L BhattJolanda M A BoerEric BoerwinkleBen BurkleyAmber BurtAravinda ChakravartiWei ChenRhonda M Cooper-DehoffSean P CurtisAlbert DreisbachDavid DugganGeorg B EhretRichard R FabsitzMyriam FornageErvin FoxClement E FurlongRon T GansevoortMarten H HofkerG Kees HovinghSusan A KirklandKandice Kottke-MarchantAbdullah KutlarAndrea Z LacroixTaimour Y LangaeeYun R LiHonghuang LinKiang LiuSteffi MaiwaldRainer MalikCARDIOGRAM, METASTROKEGurunathan MurugesanChristopher Newton-ChehJeffery R O'ConnellN Charlotte Onland-MoretWillem H OuwehandWalter PalmasBrenda W PenninxCarl J PepineMary PettingerJoseph F PolakVasan S RamachandranJane RanchalisSusan RedlinePaul M RidkerLynda M RoseHubert ScharnagNicholas J SchorkDaichi ShimboAlan R ShuldinerSathanur R SrinivasanRonald P StolkHerman A TaylorBarbara ThorandMieke D TripCornelia M van DuijnW Monique VerschurenCisca WijmengaBernhard R WinkelmannSharon WyattJ Hunter YoungBernhard O BoehmMark J CaulfieldDaniel I ChasmanKarina W DavidsonPieter A DoevendansGarret A FitzgeraldJohn G GumsHakon HakonarsonHans L HillegeThomas IlligGail P JarvikJulie A JohnsonJohn J P KasteleinWolfgang KoenigLifeLines Cohort StudyWinfried MärzBraxton D MitchellSarah S MurrayAlbertine J OldehinkelDaniel J RaderMuredach P ReillyAlex P ReinerEric E SchadtRoy L SilversteinHarold SniederAlice V StantonAndré G UitterlindenPim van der HarstYvonne T van der SchouwNilesh J SamaniAndrew D JohnsonPatricia B MunroePaul I W de BakkerXiaofeng ZhuDaniel LevyBrendan J KeatingFolkert W Asselbergs
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Free PMC article
Meta-Analysis

Loci Influencing Blood Pressure Identified Using a Cardiovascular Gene-Centric Array

Santhi K Ganesh et al. Hum Mol Genet. .
Free PMC article

Erratum in

  • Hum Mol Genet. 2013 Aug 15;22(16):3394-5. Van Setten, Jessic A [corrected to Van Setten, Jessica]

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.

Figures

Figure 1.
Figure 1.
Regional association plots of the (A) HRH1 and (B) MDM4 loci are shown with negative log10 (P-value) on the y-axis and chromosomal position on the x-axis.

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