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The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.

Accepted version
Peer-reviewed

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Type

Article

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Authors

Ehret, Georg B 
Ferreira, Teresa 
Chasman, Daniel I 
Jackson, Anne U 
Schmidt, Ellen M 

Abstract

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

Description

Keywords

Asian People, Black People, Blood Pressure, Cells, Cultured, Genome-Wide Association Study, Humans, Hypertension, Microarray Analysis, Polymorphism, Single Nucleotide

Journal Title

Nat Genet

Conference Name

Journal ISSN

1061-4036
1546-1718

Volume Title

48

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MC_UU_12015/1)
Medical Research Council (MC_UU_12015/2)
Medical Research Council (MR/N003284/1)
Medical Research Council (G1000143)
Medical Research Council (G0401527)
Medical Research Council (MR/P02811X/1)
European Commission and European Federation of Pharmaceutical Industries and Associations (EFPIA) FP7 Innovative Medicines Initiative (IMI) (116074)
Cambridge University Hospitals NHS Foundation Trust (CUH) (BRC)
British Heart Foundation (CH/12/2/29428)
Medical Research Council (MR/P013880/1)
Ume� University (unknown)
NHS Blood and Transplant (NHSBT) (WP12-01)
European Commission (279143)
NHS Blood and Transplant (NHSBT) (11-01-GEN)
Cambridge University Hospitals NHS Foundation Trust (CUH) (BRC 2012-2017)
British Heart Foundation (None)
Medical Research Council (MR/L003120/1)
European Commission (279233)
European Research Council (268834)
MRC (MR/J015709/1)
MRC (MR/J006602/1)
MRC (MR/J006599/1)
Medical Research Council (MR/M012816/1)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
British Heart Foundation (RG/16/4/32218)
Cambridge University Hospitals NHS Foundation Trust (CUH) (3819-1617-25)
Department of Health (via National Institute for Health Research (NIHR)) (NIHR BTRU-2014-10024)
Cambridge University Hospitals NHS Foundation Trust (CUH) (3819-1516-29)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
National Institute of Neurological Disorders and Stroke (R21NS064908)
National Heart Lung and Blood Institute (RC2HL101834)
Fogarty International Center (RC1TW008485)
Medical Research Council (MC_U106179472)
Medical Research Council (G0401527/1)