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 |
---|---|
Journal | Nature Genetics |
Volume | 47 |
Issue number | 11 |
Pages (from-to) | 1282-1293 |
Number of pages | 12 |
ISSN | 1061-4036 |
DOIs | |
Publication status | Published - 01.11.2015 |
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In: Nature Genetics, Vol. 47, No. 11, 01.11.2015, p. 1282-1293.
Research output: Journal Articles › Journal articles › Research › peer-review
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 - NKelly, Tanika
AU - Saleheen, Danish
AU - Lehne, Benjamin
AU - Leach, Irene Mateo
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 - Meitinger, Thomas
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 - Dorajoo, Rajkumar
AU - CHopewell, Jemma
AU - Kim, Yun Kyoung
AU - WKoivula, Robert
AU - Luan, Jian'An
AU - Lyytikäinen, Leo Pekka
AU - NNguyen, Quang
AU - Pereira, Mark A.
AU - Postmus, Iris
AU - TRaitakari, Olli
AU - Scannell Bryan, Molly
AU - Scott, Robert A.
AU - Sorice, Rossella
AU - Tragante, Vinicius
AU - Traglia, Michela
AU - White, Jon
AU - Yamamoto, Ken
AU - Zhang, Yonghong
AU - Adair, Linda S.
AU - Ahmed, Alauddin
AU - Akiyama, Koichi
AU - Asif, Rasheed
AU - Aung, Tin
AU - Barroso, Inês
AU - Bjonnes, Andrew
AU - Braun, Timothy R.
AU - Cai, Hui
AU - Chang, Li Ching
AU - Chen, Chien Hsiun
AU - Cheng, Ching Yu
AU - Chong, Yap Seng
AU - Collins, Rory
AU - Courtney, Regina
AU - Davies, Gail
AU - Delgado, Graciela
AU - Do, Loi D.
AU - Doevendans, Pieter A.
AU - Gansevoort, Ron T.
AU - Gao, Yu Tang
AU - Grammer, Tanja B.
AU - Grarup, Niels
AU - Grewal, Jagvir
AU - Gu, Dongfeng
AU - SWander, Gurpreet
AU - Hartikainen, Anna Liisa
AU - Hazen, Stanley L.
AU - He, Jing
AU - Heng, Chew Kiat
AU - Hixso, E. James Ames
AU - Hofman, Albert
AU - Hsu, Chris
AU - Huang, Wei
AU - Husemoen, Lise L.N.
AU - Hwang, Joo Yeon
AU - Ichihara, Sahoko
AU - Igase, Michiya
AU - Isono, Masato
AU - Justesen, Johanne M.
AU - Katsuya, Tomohiro
AU - GKibriya, Muhammad
AU - Kim, Young Jin
AU - Kishimoto, Miyako
AU - Koh, Woon Puay
AU - Kohara, Katsuhiko
AU - Kumari, Meena
AU - Kwek, Kenneth
AU - Lee, Nanette R.
AU - Lee, Jeannette
AU - Liao, Jiemin
AU - Lieb, Wolfgang
AU - Liewald, David C.M.
AU - Matsubara, Tatsuaki
AU - Matsushita, Yumi
AU - Meitinger, Thomas
AU - Mihailov, Evelin
AU - Milani, Lili
AU - Mills, Rebecca
AU - Mononen, Nina
AU - Müller-Nurasyid, Martina
AU - Nabika, Toru
AU - Nakashima, Eitaro
AU - Ng, Hong Kiat
AU - Nikus, Kjell
AU - Nutile, Teresa
AU - Ohkubo, Takayoshi
AU - Ohnaka, Keizo
AU - Parish, Sarah
AU - Paternoster, Lavinia
AU - Peng, Hao
AU - Peters, Annette
AU - TPham, Son
AU - Pinidiyapathirage, Mohitha J.
AU - Rahman, Mahfuzar
AU - Rakugi, Hiromi
AU - Rolandsson, Olov
AU - Rozario, Michelle Ann
AU - Ruggiero, Daniela
AU - Sala, Cinzia F.
AU - Sarju, Ralhan
AU - Shimokawa, Kazuro
AU - Snieder, Harold
AU - SparsØ, Thomas
AU - Spiering, Wilko
AU - Starr, John M.
AU - Stott, David J.
AU - OStram, Daniel
AU - Sugiyama, Takao
AU - Szymczak, Silke
AU - Tang, W. H.Wilson
AU - Tong, Lin
AU - Trompet, Stella
AU - Turjanmaa, Väinö
AU - Ueshima, Hirotsugu
AU - Uitterlinden, André G.
AU - Umemura, Satoshi
AU - Vaarasmaki, Marja
AU - Dam, Rob Mvan
AU - Van Gilst, Wiek H.
AU - Van Veldhuisen, Dirk J.
AU - Viikari, Jorma S.
AU - Waldenberger, Melanie
AU - Wang, Yiqin
AU - Wang, Aili
AU - Wilson, Rory
AU - Wong, Tien Yin
AU - Xiang, Yong Bing
AU - Yamaguchi, Shuhei
AU - Ye, Xingwang
AU - Young, Robin D.
AU - Young, Terri L.
AU - Yuan, Jian Min
AU - Zhou, Xueya
AU - Asselbergs, Folkert W.
AU - Ciullo, Marina
AU - Clarke, Robert
AU - Deloukas, Panos
AU - Franke, Andre
AU - Paul, W. Frank
AU - Franks, Steve
AU - Friedlander, Yechiel
AU - Gross, Myron D.
AU - Guo, Zhirong
AU - Hansen, Torben
AU - Jarvelin, Marjo Riitta
AU - JØrgensen, Torben
AU - Jukema, J. Wouter
AU - Kähönen, Mika
AU - Kajio, Hiroshi
AU - Kivimaki, Mika
AU - Lee, Jong Young
AU - Lehtimäki, Terho
AU - Linneberg, Allan
AU - Miki, Tetsuro
AU - Pedersen, Oluf
AU - Samani, Nilesh J.
AU - SØrensen, Thorkild I.A.
AU - Takayanagi, Ryoichi
AU - Toniolo, Daniela
AU - Ahsan, Habibul
AU - Allayee, Hooman
AU - Chen, Yuan Tsong
AU - Danesh, John
AU - Deary, Ian J.
AU - Franco, Oscar H.
AU - Franke, Lude
AU - THeijman, Bastiaan
AU - Holbrook, Joanna D.
AU - Isaacs, Aaron
AU - Kim, Bong Jo
AU - Lin, Xu
AU - Liu, Jianjun
AU - März, Winfried
AU - Metspalu, Andres
AU - Mohlke, Karen L.
AU - Sangher, K.
AU - Harambir, Dharambir
AU - Shu, Xiao Ou
AU - Van Meurs, Joyce B.J.
AU - Vithana, Eranga
AU - Wickremasinghe, Ananda R.
AU - Wijmenga, Cisca
AU - Wolffenbuttel, Bruce H.W.
AU - Yokota, Mitsuhiro
AU - Zheng, Wei
AU - Zhu, Dingliang
AU - Vineis, Paolo
AU - Kyrtopoulos, Soterios A.
AU - Kleinjans, Jos C.S.
AU - McCarthy, Mark I.
AU - Soong, Richie
AU - Gieger, Christian
AU - Scott, James
AU - Teo, Yik Ying
AU - He, Jiang
AU - Elliott, Paul
AU - Tai, E. Shyong
AU - Van Der Harst, Pim
AU - Kooner, Jaspal S.
AU - Chambers, John C.
N1 - Publisher Copyright: © 2015 Nature America, Inc.
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.
UR - http://www.scopus.com/inward/record.url?scp=84965118964&partnerID=8YFLogxK
U2 - 10.1038/ng.3405
DO - 10.1038/ng.3405
M3 - Journal articles
C2 - 26390057
AN - SCOPUS:84965118964
SN - 1061-4036
VL - 47
SP - 1282
EP - 1293
JO - Nature Genetics
JF - Nature Genetics
IS - 11
ER -