Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation. / Kato, Norihiro; Loh, Marie; Takeuchi, Fumihiko; Verweij, Niek; Wang, Xu; Zhang, Weihua; Kelly, Tanika N; Saleheen, Danish; Lehne, Benjamin; Mateo Leach, Irene; Drong, Alexander W; Abbott, James; Wahl, Simone; Tan, Sian-Tsung; Scott, William R; Campanella, Gianluca; Chadeau-Hyam, Marc; Afzal, Uzma; Ahluwalia, Tarun Veer Singh; Bonder, Marc Jan; Chen, Peng; Dehghan, Abbas; Edwards, Todd L; Esko, Tõnu; Go, Min Jin; Harris, Sarah E; Hartiala, Jaana; Kasela, Silva; Kasturiratne, Anuradhani; Khor, Chiea-Chuen; Kleber, Marcus E; Li, Huaixing; Mok, Zuan Yu; Nakatochi, Masahiro; Sapari, Nur Sabrina; Saxena, Richa; Stewart, Alexandre F R; Stolk, Lisette; Tabara, Yasuharu; Teh, Ai Ling; Wu, Ying; Wu, Jer-Yuarn; Grarup, Niels; Justesen, Johanne M; Sparsø, Thomas Hempel; Hansen, Torben; Jørgensen, Torben; Linneberg, Allan; Pedersen, Oluf; Sørensen, Thorkild I A; BIOS Consortium.
In: Nature Genetics, Vol. 47, No. 11, 2015, p. 1282-93.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
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
Y1 - 2015
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
VL - 47
SP - 1282
EP - 1293
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 11
ER -
ID: 150707635