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

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; Tarun Veer Singh 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; Niels Grarup; Johanne M Justesen; Thomas Hempel Sparsø; Torben Hansen; Torben Jørgensen; Allan Linneberg; Oluf Pedersen; Thorkild I A Sørensen; BIOS Consortium

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

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, Tarun Veer Singh Ahluwalia, Marc Jan BonderPeng 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, Niels Grarup, Johanne M Justesen, Thomas Hempel Sparsø, Torben Hansen, Torben Jørgensen, Allan Linneberg, Oluf Pedersen, Thorkild I A Sørensen, BIOS Consortium

176 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	47
Udgave nummer	11
Sider (fra-til)	1282-93
Antal sider	12
ISSN	1061-4036
DOI	https://doi.org/10.1038/ng.3405
Status	Udgivet - 1 nov. 2015

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10.1038/ng.3405

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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., Ahluwalia, T. V. S., ... BIOS Consortium (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

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, TVS, 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, Grarup, N , Justesen, JM, Sparsø, TH, Hansen, T, Jørgensen, T, Linneberg, A , Pedersen, O , Sørensen, TIA & BIOS Consortium 2015, 'Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation', Nature Genetics, bind 47, nr. 11, s. 1282-93. https://doi.org/10.1038/ng.3405

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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 = "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, {Tarun Veer Singh} 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 Niels Grarup and Justesen, {Johanne M} and Spars{\o}, {Thomas Hempel} and Torben Hansen and Torben J{\o}rgensen and Allan Linneberg and Oluf Pedersen and S{\o}rensen, {Thorkild I A} and {BIOS Consortium}",

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doi = "10.1038/ng.3405",

language = "English",

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

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, Tarun Veer Singh

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 - Grarup, Niels

AU - Justesen, Johanne M

AU - Sparsø, Thomas Hempel

AU - Hansen, Torben

AU - Jørgensen, Torben

AU - Linneberg, Allan

AU - Pedersen, Oluf

AU - Sørensen, Thorkild I A

AU - BIOS Consortium

PY - 2015/11/1

Y1 - 2015/11/1

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 - Journal 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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