Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

BIOS-consortium; Norihiro Kato; Marie Loh; Fumihiko Takeuchi; Niek Verweij; Xu Wang; Weihua Zhang; Tanika N Kelly; Danish Saleheen; Benjamin Lehne; Irene Mateo Leach; Alexander W Drong; James Abbott; Simone Wahl; Sian-Tsung Tan; William R Scott; Gianluca Campanella; Marc Chadeau-Hyam; Uzma Afzal; Tarunveer S Ahluwalia; Marc Jan Bonder; Peng Chen; Abbas Dehghan; Todd L Edwards; Tõnu Esko; Min Jin Go; Sarah E Harris; Jaana Hartiala; Silva Kasela; Anuradhani Kasturiratne; Chiea-Chuen Khor; Marcus E Kleber; Huaixing Li; Zuan Yu Mok; Masahiro Nakatochi; Nur Sabrina Sapari; Richa Saxena; Alexandre F R Stewart; Lisette Stolk; Yasuharu Tabara; Ai Ling Teh; Ying Wu; Jer-Yuarn Wu; Yi Zhang; Imke Aits; Alexessander Da Silva Couto Alves; Shikta Das; Gail Davies; David C M Liewald; John M Starr; Ian J Deary

doi:10.1038/ng.3405

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

BIOS-consortium, Norihiro Kato, Marie Loh, Fumihiko Takeuchi, Niek Verweij, Xu Wang, Weihua Zhang, Tanika N Kelly, Danish Saleheen, Benjamin Lehne, Irene Mateo Leach, Alexander W Drong, James Abbott, Simone Wahl, Sian-Tsung Tan, William R Scott, Gianluca Campanella, Marc Chadeau-Hyam, Uzma Afzal, Tarunveer S AhluwaliaMarc Jan Bonder, Peng Chen, Abbas Dehghan, Todd L Edwards, Tõnu Esko, Min Jin Go, Sarah E Harris, Jaana Hartiala, Silva Kasela, Anuradhani Kasturiratne, Chiea-Chuen Khor, Marcus E Kleber, Huaixing Li, Zuan Yu Mok, Masahiro Nakatochi, Nur Sabrina Sapari, Richa Saxena, Alexandre F R Stewart, Lisette Stolk, Yasuharu Tabara, Ai Ling Teh, Ying Wu, Jer-Yuarn Wu, Yi Zhang, Imke Aits, Alexessander Da Silva Couto Alves, Shikta Das, Gail Davies, David C M Liewald, John M Starr, Ian J Deary

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1282-93
Number of pages	12
Journal	Nature Genetics
Volume	47
Issue number	11
DOIs	https://doi.org/10.1038/ng.3405
Publication status	Published - 21 Sept 2015

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10.1038/ng.3405

RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.
Deary, I., Gale, C., Holmes, M., Logie, P., Maclullich, A., Porteous, D., Seckl, J., Starr, J., Wardlaw, J. & Okely, J.
1/09/13 → 31/08/19
Project: Research
A Hundred at Ninety: the common cause Hypothesis of Ageing tested in four waves of the Lothian Birth Cohort 1921
Deary, I., Bates, T., Gow, A. & Starr, J.
UK central government bodies/local authorities, health and hospital authorities
1/01/11 → 31/12/12
Project: Research
A genome wide association study of non pathological cognitive ageing
Deary, I., Porteous, D. & Tenesa, A.
BBSRC
1/09/08 → 31/08/10
Project: Research

Cite this

BIOS-consortium, Kato, N., Loh, M., Takeuchi, F., Verweij, N., Wang, X., Zhang, W., Kelly, T. N., Saleheen, D., Lehne, B., Mateo Leach, I., Drong, A. W., Abbott, J., Wahl, S., Tan, S.-T., Scott, W. R., Campanella, G., Chadeau-Hyam, M., Afzal, U., ... Deary, I. J. (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), 1282-93. https://doi.org/10.1038/ng.3405

@article{3f54687e29824f4b8ea2c83fbde5843a,

title = "Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation",

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.",

author = "BIOS-consortium and Norihiro Kato and Marie Loh and Fumihiko Takeuchi and Niek Verweij and Xu Wang and Weihua Zhang and Kelly, {Tanika N} and Danish Saleheen and Benjamin Lehne and {Mateo Leach}, Irene and Drong, {Alexander W} and James Abbott and Simone Wahl and Sian-Tsung Tan and Scott, {William R} and Gianluca Campanella and Marc Chadeau-Hyam and Uzma Afzal and Ahluwalia, {Tarunveer S} and Bonder, {Marc Jan} and Peng Chen and Abbas Dehghan and Edwards, {Todd L} and T{\~o}nu Esko and Go, {Min Jin} and Harris, {Sarah E} and Jaana Hartiala and Silva Kasela and Anuradhani Kasturiratne and Chiea-Chuen Khor and Kleber, {Marcus E} and Huaixing Li and Mok, {Zuan Yu} and Masahiro Nakatochi and Sapari, {Nur Sabrina} and Richa Saxena and Stewart, {Alexandre F R} and Lisette Stolk and Yasuharu Tabara and Teh, {Ai Ling} and Ying Wu and Jer-Yuarn Wu and Yi Zhang and Imke Aits and {Da Silva Couto Alves}, Alexessander and Shikta Das and Gail Davies and Liewald, {David C M} and Starr, {John M} and Deary, {Ian J}",

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day = "21",

doi = "10.1038/ng.3405",

language = "English",

volume = "47",

pages = "1282--93",

journal = "Nature Genetics",

issn = "1061-4036",

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BIOS-consortium, Kato, N, Loh, M, Takeuchi, F, Verweij, N, Wang, X, Zhang, W, Kelly, TN, Saleheen, D, Lehne, B, Mateo Leach, I, Drong, AW, Abbott, J, Wahl, S, Tan, S-T, Scott, WR, Campanella, G, Chadeau-Hyam, M, Afzal, U, Ahluwalia, TS, Bonder, MJ, Chen, P, Dehghan, A, Edwards, TL, Esko, T, Go, MJ, Harris, SE, Hartiala, J, Kasela, S, Kasturiratne, A, Khor, C-C, Kleber, ME, Li, H, Mok, ZY, Nakatochi, M, Sapari, NS, Saxena, R, Stewart, AFR, Stolk, L, Tabara, Y, Teh, AL, Wu, Y, Wu, J-Y, Zhang, Y, Aits, I, Da Silva Couto Alves, A, Das, S, Davies, G, Liewald, DCM, Starr, JM & Deary, IJ 2015, 'Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation', Nature Genetics, vol. 47, no. 11, pp. 1282-93. https://doi.org/10.1038/ng.3405

TY - JOUR

T1 - Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

AU - BIOS-consortium

AU - Kato, Norihiro

AU - Loh, Marie

AU - Takeuchi, Fumihiko

AU - Verweij, Niek

AU - Wang, Xu

AU - Zhang, Weihua

AU - Kelly, Tanika N

AU - Saleheen, Danish

AU - Lehne, Benjamin

AU - Mateo Leach, Irene

AU - Drong, Alexander W

AU - Abbott, James

AU - Wahl, Simone

AU - Tan, Sian-Tsung

AU - Scott, William R

AU - Campanella, Gianluca

AU - Chadeau-Hyam, Marc

AU - Afzal, Uzma

AU - Ahluwalia, Tarunveer S

AU - Bonder, Marc Jan

AU - Chen, Peng

AU - Dehghan, Abbas

AU - Edwards, Todd L

AU - Esko, Tõnu

AU - Go, Min Jin

AU - Harris, Sarah E

AU - Hartiala, Jaana

AU - Kasela, Silva

AU - Kasturiratne, Anuradhani

AU - Khor, Chiea-Chuen

AU - Kleber, Marcus E

AU - Li, Huaixing

AU - Mok, Zuan Yu

AU - Nakatochi, Masahiro

AU - Sapari, Nur Sabrina

AU - Saxena, Richa

AU - Stewart, Alexandre F R

AU - Stolk, Lisette

AU - Tabara, Yasuharu

AU - Teh, Ai Ling

AU - Wu, Ying

AU - Wu, Jer-Yuarn

AU - Zhang, Yi

AU - Aits, Imke

AU - Da Silva Couto Alves, Alexessander

AU - Das, Shikta

AU - Davies, Gail

AU - Liewald, David C M

AU - Starr, John M

AU - Deary, Ian J

PY - 2015/9/21

Y1 - 2015/9/21

N2 - 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.

AB - 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.

U2 - 10.1038/ng.3405

DO - 10.1038/ng.3405

M3 - Article

C2 - 26390057

SN - 1061-4036

VL - 47

SP - 1282

EP - 1293

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

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Projects

RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.

A Hundred at Ninety: the common cause Hypothesis of Ageing tested in four waves of the Lothian Birth Cohort 1921

A genome wide association study of non pathological cognitive ageing

Cite this