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

Ehret, GB; Ferreira, T; Chasman, DI; Jackson, AU; Schmidt, EM; Johnson, T; Thorleifsson, G; Luan, J; Donnelly, LA; Kanoni, S; Petersen, AK; Pihur, V; Strawbridge, RJ; Shungin, D; Hughes, MF; Meirelles, O; Kaakinen, M; Bouatia-Naji, N; Kristiansson, K; Shah, S

doi:https://www.dx.doi.org/10.1038/ng.3667

File(s)

Genetic of BP regs & its target organs....Ehret GH et al final submitted version_01a_NG-A41405R_manuscript_finalCLEAN.docx (554.25 KB)

Accepted version

Author(s)

Ehret, GB

Ferreira, T

Chasman, DI

Jackson, AU

Schmidt, EM

more

Type

Journal Article

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.

Date Issued

2016-09-12

Date Acceptance

2016-08-15

Citation

Nature Genetics, 2016, 48, pp.1171-1184

URI

http://hdl.handle.net/10044/1/48175

DOI

https://www.dx.doi.org/10.1038/ng.3667

ISSN

1546-1718

Publisher

Nature Publishing Group

Start Page

1171

End Page

1184

Journal / Book Title

Nature Genetics

Volume

48

Copyright Statement

Sponsor

National Institute for Health Research

Medical Research Council (MRC)

Grant Number

NF-SI-0611-10136

MR/L01341X/1

Subjects

Science & Technology

Life Sciences & Biomedicine

Genetics & Heredity

GENOME-WIDE ASSOCIATION

ARTERIAL-HYPERTENSION

COMMON VARIANTS

CELL-TYPES

LOCI

TRAITS

CHROMATIN

SUSCEPTIBILITY

METAANALYSIS

BIOLOGY

African Continental Ancestry Group

Asian Continental Ancestry Group

Blood Pressure

Cells, Cultured

Genome-Wide Association Study

Humans

Hypertension

Microarray Analysis

Polymorphism, Single Nucleotide

CHARGE-EchoGen Consortium

CHARGE-HF Consortium

Wellcome Trust Case Control Consortium

Developmental Biology

11 Medical And Health Sciences

06 Biological Sciences

Publication Status

Published