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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
Authors :
Kato, Norihiro Loh, Marie Takeuchi, Fumihiko Verweij, Niek Wang, Xu Zhang, Weihua Kelly, Tanika N. Saleheen, Danish Lehne, Benjamin Leach, Irene Mateo Drong, Alexander W. Abbott, James Wahl, Simone Tan, Sian-Tsung Scott, William R. Campanella, Gianluca Chadeau-Hyam, Marc Afzal, Uzma Ahluwalia, Tarunveer S. Bonder, Marc Jan Chen, Peng Dehghan, Abbas Edwards, Todd L. Esko, Tonu 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 Zhang, Yi Aits, Imke Alves, Alexessander Da Silva Couto Das, Shikta Dorajoo, Rajkumar Hopewell, Jemma C. Kim, Yun Kyoung Koivula, Robert W. Luan, Jian'an Lyytikainen, Leo-Pekka Nguyen, Quang N. Pereira, Mark A. Postmus, Iris Raitakari, Olli T. Bryan, Molly Scannell Scott, Robert A. Sorice, Rossella Tragante, Vinicius Traglia, Michela White, Jon Yamamoto, Ken Zhang, Yonghong Adair, Linda S. Ahmed, Alauddin Akiyama, Koichi Asif, Rasheed Aung, Tin Barroso, Ines Bjonnes, Andrew Braun, Timothy R. Cai, Hui Chang, Li-Ching Chen, Chien-Hsiun Cheng, Ching-Yu Chong, Yap-Seng Collins, Rory Courtney, Regina Davies, Gail Delgado, Graciela Do, Loi D. Doevendans, Pieter A. Gansevoort, Ron T. Gao, Yu-Tang Grammer, Tanja B. Grarup, Niels Grewal, Jagvir Gu, Dongfeng Wander, Gurpreet S. Hartikainen, Anna-Liisa Hazen, Stanley L. He, Jing Heng, Chew-Kiat Hixson, James E. Hofman, Albert Hsu, Chris Huang, Wei Husemoen, Lise L. N. Hwang, Joo-Yeon Ichihara, Sahoko Igase, Michiya Isono, Masato Justesen, Johanne M. Katsuy, Tomohiro Kibriya, Muhammad G. Kim, Young Jin Kishimoto, Miyako Koh, Woon-Puay Kohara, Katsuhiko Kumari, Meena Kwek, Kenneth Lee, Nanette R. Lee, Jeannette Liao, Jiemin Lieb, Wolfgang Liewald, David C. M. Matsubara, Tatsuaki Matsushita, Yumi Meitinger, Thomas Mihailov, Evelin Milani, Lili Mills, Rebecca Mononen, Nina Mueller-Nurasyid, Martina Nabika, Toru Nakashima, Eitaro Ng, Hong Kiat Nikus, Kjell Nutile, Teresa Ohkubo, Takayoshi Ohnaka, Keizo Parish, Sarah Paternoster, Lavinia Peng, Hao Peters, Annette Pham, Son T. Pinidiyapathirage, Mohitha J. Rahman, Mahfuzar Rakugi, Hiromi Rolandsson, Olov Rozario, Michelle Ann Ruggiero, Daniela Sala, Cinzia F. Sarju, Ralhan Shimokawa, Kazuro Snieder, Harold Sparso, Thomas Spiering, Wilko Starr, John M. Stott, David J. Stram, Daniel O. Sugiyama, Takao Szymczak, Silke Tang, W. H. Wilson Tong, Lin Trompet, Stella Turjanmaa, Vaino Ueshima, Hirotsugu Uitterlinden, Andre G. Umemura, Satoshi Vaarasmaki, Marja van Dam, Rob M. van Gilst, Wiek H. van Veldhuisen, Dirk J. Viikari, Jorma S. Waldenberger, Melanie Wang, Yiqin Wang, Aili Wilson, Rory Wong, Tien-Yin Xiang, Yong-Bing Yamaguchi, Shuhei Ye, Xingwang Young, Robin D. Young, Terri L. Yuan, Jian-Min Zhou, Xueya Asselbergs, Folkert W. Ciullo, Marina Clarke, Robert Deloukas, Panos Franke, Andre Franks, Paul W Franks, Steve Friedlander, Yechiel Gross, Myron D. Guo, Zhirong Hansen, Torben Jarvelin, Marjo-Riitta Jorgensen, Torben Jukema, J. Wouter Kahonen, Mika Kajio, Hiroshi Kivimaki, Mika Lee, Jong-Young Lehtimaki, Terho Linneberg, Allan Miki, Tetsuro Pedersen, Oluf Samani, Nilesh J. Sorensen, Thorkild I. A. Takayanagi, Ryoichi Toniolo, Daniela Ahsan, Habibul Allayee, Hooman Chen, Yuan-Tsong Danesh, John Deary, Ian J. Franco, Oscar H. Franke, Lude Heijman, Bastiaan T. Holbrook, Joanna D. Isaacs, Aaron Kim, Bong-Jo Lin, Xu Liu, Jianjun Maerz, Winfried Metspalu, Andres Mohlke, Karen L. Sanghera, Dharambir K. Shu, Xiao-Ou van Meurs, Joyce B. J. Vithana, Eranga Wickremasinghe, Ananda R. Wijmenga, Cisca Wolffenbuttel, Bruce H. W. Yokota, Mitsuhiro Zheng, Wei Zhu, Dingliang Vineis, Paolo Kyrtopoulos, Soterios A. Kleinjans, Jos C. S. McCarthy, Mark I. Soong, Richie Gieger, Christian Scott, James Teo, Yik-Ying He, Jiang Elliott, Paul Tai, E. Shyong van der Harst, Pim Kooner, Jaspal S. Chambers, John C. Kato, Norihiro Loh, Marie Takeuchi, Fumihiko Verweij, Niek Wang, Xu Zhang, Weihua Kelly, Tanika N. Saleheen, Danish Lehne, Benjamin Leach, Irene Mateo Drong, Alexander W. Abbott, James Wahl, Simone Tan, Sian-Tsung Scott, William R. Campanella, Gianluca Chadeau-Hyam, Marc Afzal, Uzma Ahluwalia, Tarunveer S. Bonder, Marc Jan Chen, Peng Dehghan, Abbas Edwards, Todd L. Esko, Tonu 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 Zhang, Yi Aits, Imke Alves, Alexessander Da Silva Couto Das, Shikta Dorajoo, Rajkumar Hopewell, Jemma C. Kim, Yun Kyoung Koivula, Robert W. Luan, Jian'an Lyytikainen, Leo-Pekka Nguyen, Quang N. Pereira, Mark A. Postmus, Iris Raitakari, Olli T. Bryan, Molly Scannell Scott, Robert A. Sorice, Rossella Tragante, Vinicius Traglia, Michela White, Jon Yamamoto, Ken Zhang, Yonghong Adair, Linda S. Ahmed, Alauddin Akiyama, Koichi Asif, Rasheed Aung, Tin Barroso, Ines Bjonnes, Andrew Braun, Timothy R. Cai, Hui Chang, Li-Ching Chen, Chien-Hsiun Cheng, Ching-Yu Chong, Yap-Seng Collins, Rory Courtney, Regina Davies, Gail Delgado, Graciela Do, Loi D. Doevendans, Pieter A. Gansevoort, Ron T. Gao, Yu-Tang Grammer, Tanja B. Grarup, Niels Grewal, Jagvir Gu, Dongfeng Wander, Gurpreet S. Hartikainen, Anna-Liisa Hazen, Stanley L. He, Jing Heng, Chew-Kiat Hixson, James E. Hofman, Albert Hsu, Chris Huang, Wei Husemoen, Lise L. N. Hwang, Joo-Yeon Ichihara, Sahoko Igase, Michiya Isono, Masato Justesen, Johanne M. Katsuy, Tomohiro Kibriya, Muhammad G. Kim, Young Jin Kishimoto, Miyako Koh, Woon-Puay Kohara, Katsuhiko Kumari, Meena Kwek, Kenneth Lee, Nanette R. Lee, Jeannette Liao, Jiemin Lieb, Wolfgang Liewald, David C. M. Matsubara, Tatsuaki Matsushita, Yumi Meitinger, Thomas Mihailov, Evelin Milani, Lili Mills, Rebecca Mononen, Nina Mueller-Nurasyid, Martina Nabika, Toru Nakashima, Eitaro Ng, Hong Kiat Nikus, Kjell Nutile, Teresa Ohkubo, Takayoshi Ohnaka, Keizo Parish, Sarah Paternoster, Lavinia Peng, Hao Peters, Annette Pham, Son T. Pinidiyapathirage, Mohitha J. Rahman, Mahfuzar Rakugi, Hiromi Rolandsson, Olov Rozario, Michelle Ann Ruggiero, Daniela Sala, Cinzia F. Sarju, Ralhan Shimokawa, Kazuro Snieder, Harold Sparso, Thomas Spiering, Wilko Starr, John M. Stott, David J. Stram, Daniel O. Sugiyama, Takao Szymczak, Silke Tang, W. H. Wilson Tong, Lin Trompet, Stella Turjanmaa, Vaino Ueshima, Hirotsugu Uitterlinden, Andre G. Umemura, Satoshi Vaarasmaki, Marja van Dam, Rob M. van Gilst, Wiek H. van Veldhuisen, Dirk J. Viikari, Jorma S. Waldenberger, Melanie Wang, Yiqin Wang, Aili Wilson, Rory Wong, Tien-Yin Xiang, Yong-Bing Yamaguchi, Shuhei Ye, Xingwang Young, Robin D. Young, Terri L. Yuan, Jian-Min Zhou, Xueya Asselbergs, Folkert W. Ciullo, Marina Clarke, Robert Deloukas, Panos Franke, Andre Franks, Paul W Franks, Steve Friedlander, Yechiel Gross, Myron D. Guo, Zhirong Hansen, Torben Jarvelin, Marjo-Riitta Jorgensen, Torben Jukema, J. Wouter Kahonen, Mika Kajio, Hiroshi Kivimaki, Mika Lee, Jong-Young Lehtimaki, Terho Linneberg, Allan Miki, Tetsuro Pedersen, Oluf Samani, Nilesh J. Sorensen, Thorkild I. A. Takayanagi, Ryoichi Toniolo, Daniela Ahsan, Habibul Allayee, Hooman Chen, Yuan-Tsong Danesh, John Deary, Ian J. Franco, Oscar H. Franke, Lude Heijman, Bastiaan T. Holbrook, Joanna D. Isaacs, Aaron Kim, Bong-Jo Lin, Xu Liu, Jianjun Maerz, Winfried Metspalu, Andres Mohlke, Karen L. Sanghera, Dharambir K. Shu, Xiao-Ou van Meurs, Joyce B. J. Vithana, Eranga Wickremasinghe, Ananda R. Wijmenga, Cisca Wolffenbuttel, Bruce H. W. Yokota, Mitsuhiro Zheng, Wei Zhu, Dingliang Vineis, Paolo Kyrtopoulos, Soterios A. Kleinjans, Jos C. S. McCarthy, Mark I. Soong, Richie Gieger, Christian Scott, James Teo, Yik-Ying He, Jiang Elliott, Paul Tai, E. Shyong van der Harst, Pim Kooner, Jaspal S. Chambers, John C.
Publication Year :
2015
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.
Details
Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1233713859
Document Type :
Electronic Resource
Full Text :
https://doi.org/10.1038.ng.3405