Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
Kato, N.
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Loh, M.
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Takeuchi, F.
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Verweij, N.
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Go, M.J.
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Couto Alves, Alexessander
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al, et
df099e87-31d7-4ccf-a9fa-b92a380537f9
21 September 2015
Kato, N.
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Loh, M.
525f9ca2-b7b4-4a60-9f5b-eebed4e38db2
Takeuchi, F.
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Verweij, N.
e44c13e0-b434-4f15-8503-c7a3f7fa3258
Go, M.J.
b481bdb5-ac86-4506-a225-f3a385aa7d14
Couto Alves, Alexessander
87b9179e-abde-4ca5-abfc-4b7c5ac8b03b
al, et
df099e87-31d7-4ccf-a9fa-b92a380537f9
Kato, N., Loh, M., Takeuchi, F., Verweij, N., Go, M.J., Couto Alves, Alexessander and al, et
(2015)
Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.
Nature Genetics, 47 (11).
(doi:10.1038/ng.3405).
Abstract
We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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Accepted/In Press date: 21 August 2015
Published date: 21 September 2015
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Local EPrints ID: 494859
URI: http://eprints.soton.ac.uk/id/eprint/494859
ISSN: 1061-4036
PURE UUID: 1c8df344-7620-488b-93f6-47b580ee31a3
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Date deposited: 18 Oct 2024 16:30
Last modified: 30 Oct 2024 03:10
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Author:
N. Kato
Author:
M. Loh
Author:
F. Takeuchi
Author:
N. Verweij
Author:
M.J. Go
Author:
Alexessander Couto Alves
Author:
et al
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