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Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Abstract

Blood pressure is a heritable trait1 influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure)2. Even small increments in blood pressure are associated with an increased risk of cardiovascular events3. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3GUCY1B3, NPR3C5orf23, ADM, FURINFES, GOSR2, GNASEDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

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Figure 1: Genome-wide −log 10 P -value plots and effects for significant loci.

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Acknowledgements

A number of the participating studies and authors are members of the CHARGE and Global BPgen consortia. Many funding mechanisms by NIH/NHLBI, European and private funding agencies contributed to this work and a full list is provided in section 21 of the Supplementary Materials.

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Full author contributions and roles are listed in Supplementary Materials section 19.

Corresponding authors

Correspondence to Patricia B. Munroe, Aravinda Chakravarti, Christopher Newton-Cheh, Daniel Levy or Mark J. Caulfield.

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The author declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Text, legends for Supplementary Tables 1-14 (see separate file Supplementary Tables file (“ICBPresub4_SoMtables_final.xls”), Supplementary Table 15, Supplementary Figures 1-6 with legends, Supplementary Reference, Author Contributions and Acknowledgements (see Contents for more details). (PDF 13542 kb)

Supplementary Tables

This file (“ICBPresub4_SoMtables_final.xls”) contains Supplementary Tables 1-14 (see Supplementary Information files for legends). (XLS 234 kb)

Supplementary Data

This zipped file (“ICBP-summary-Nature.csv”) contains the genome-wide meta-analysis p-values. The definitions of the variables are as follows: rsid: SNP ID (rs number); chr.hg18: chromosome; pos.hg18: physical position in hg18 coordinates; pval.GC.SBP: genome-wide meta-analysis p-values for systolic blood pressure, corrected for genomic control; pval.GC.DBP: genome-wide meta-analysis p-values for diastolic blood pressure, corrected for genomic control. This file was replaced on 07 October 2011. Should you experience a problem opening this file please go to the following link http://www.georgehretlab.org/icbp_088023401234-9812599.html (please choose Supplementary Materials: Data file (genome-wide pvals) - the other files are old versions). (ZIP 28365 kb)

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The International Consortium for Blood Pressure Genome-Wide Association Studies. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478, 103–109 (2011). https://doi.org/10.1038/nature10405

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