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Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.;Isfahan Univ Med Sci, Res Inst Primordial Prevent Noncommunicable Dis, Tehran, Iran..
Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Neurosci Campus Amsterdam, Amsterdam, Netherlands..
Harvard Med Sch, Hebrew SeniorLife, Boston, MA USA.;Framingham Heart Dis Epidemiol Study, Natl Heart Lung & Blood Inst, Framingham, MA USA..
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2017 (English)In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 70, no 3, E4-e19 p.Article in journal (Refereed) Published
Abstract [en]

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.

Place, publisher, year, edition, pages
2017. Vol. 70, no 3, E4-e19 p.
Keyword [en]
blood pressure, cardiovascular risk, complex traits, eSNP, GWAS, hypertension
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-334925DOI: 10.1161/HYPERTENSIONAHA.117.09438ISI: 000407241500001OAI: oai:DiVA.org:uu-334925DiVA: diva2:1161293
Funder
NIH (National Institute of Health), R01-DK062370; ZIA-HG000024; R01D0042157-01A; MH081802; 1RC2 MH089951; 1RC2 MH089995Swedish Research Council, K2007-66X-20270-01-3; 2011-5252; 2012-2884; 2011-2354; 2015-03327EU, FP7, Seventh Framework Programme, FP7 313010EU, European Research CouncilSwedish Heart Lung Foundation, 20120197Torsten Söderbergs stiftelseKnut and Alice Wallenberg FoundationSwedish Research Council, 2012-1397; M-2005-1112; 2009-2298Swedish Diabetes Association, 2013-024Swedish Society for Medical Research (SSMF)
Available from: 2017-11-29 Created: 2017-11-29 Last updated: 2017-11-29Bibliographically approved

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Enroth, StefanGiedraitis, VilmantasJohansson, ÅsaLind, LarsSundström, JohanGyllensten, UlfIngelsson, Erik

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Enroth, StefanGiedraitis, VilmantasJohansson, ÅsaLind, LarsSundström, JohanGyllensten, UlfIngelsson, Erik
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Medicinsk genetik och genomikScience for Life Laboratory, SciLifeLabGeriatricsCardiovascular epidemiologyMolecular epidemiology
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