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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 and Leach, Irene Mateo, et al. (2015) In Nature Genetics 47(11). p.93-1282
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... (More)
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. (Less)
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Nature Genetics
volume
47
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11
pages
93 - 1282
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Nature Publishing Group
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  • pmid:26390057
  • wos:000363988200012
  • scopus:84965118964
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1546-1718
DOI
10.1038/ng.3405
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English
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yes
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394f2772-061c-4358-a79c-69b1adf24c52 (old id 8035521)
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http://www.ncbi.nlm.nih.gov/pubmed/26390057?dopt=Abstract
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2015-10-03 17:57:02
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@article{394f2772-061c-4358-a79c-69b1adf24c52,
  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       = {Kato, Norihiro and Loh, Marie and Takeuchi, Fumihiko and Verweij, Niek and Wang, Xu and Zhang, Weihua and Kelly, Tanika N and Saleheen, Danish and Lehne, Benjamin and Leach, Irene Mateo and Drong, Alexander W and Abbott, James and Wahl, Simone and Tan, Sian-Tsung and Scott, William R and Campanella, Gianluca and Chadeau-Hyam, Marc and Afzal, Uzma and Ahluwalia, Tarunveer S and Bonder, Marc Jan and Chen, Peng and Dehghan, Abbas and Edwards, Todd L and Esko, Tõnu and Go, Min Jin and Harris, Sarah E and Hartiala, Jaana and Kasela, Silva and Kasturiratne, Anuradhani and Khor, Chiea-Chuen and Kleber, Marcus E and Li, Huaixing and Mok, Zuan Yu and Nakatochi, Masahiro and Sapari, Nur Sabrina and Saxena, Richa and Stewart, Alexandre F R and Stolk, Lisette and Tabara, Yasuharu and Teh, Ai Ling and Wu, Ying and Wu, Jer-Yuarn and Zhang, Yi and Aits, Imke and Da Silva Couto Alves, Alexessander and Das, Shikta and Dorajoo, Rajkumar and Hopewell, Jemma C and Kim, Yun Kyoung and Koivula, Robert and Luan, Jian'an and Lyytikäinen, Leo-Pekka and Nguyen, Quang N and Pereira, Mark A and Postmus, Iris and Raitakari, Olli T and Bryan, Molly Scannell and Scott, Robert A and Sorice, Rossella and Tragante, Vinicius and Traglia, Michela and White, Jon and Yamamoto, Ken and Zhang, Yonghong and Adair, Linda S and Ahmed, Alauddin and Akiyama, Koichi and Asif, Rasheed and Aung, Tin and Barroso, Inês and Bjonnes, Andrew and Braun, Timothy R and Cai, Hui and Chang, Li-Ching and Chen, Chien-Hsiun and Cheng, Ching-Yu and Chong, Yap-Seng and Collins, Rory and Courtney, Regina and Davies, Gail and Delgado, Graciela and Do, Loi D and Doevendans, Pieter A and Gansevoort, Ron T and Gao, Yu-Tang and Grammer, Tanja B and Grarup, Niels and Grewal, Jagvir and Gu, Dongfeng and Wander, Gurpreet S and Hartikainen, Anna-Liisa and Hazen, Stanley L and He, Jing and Heng, Chew-Kiat and Hixson, James E and Hofman, Albert and Hsu, Chris and Huang, Wei and Husemoen, Lise L N and Hwang, Joo-Yeon and Ichihara, Sahoko and Igase, Michiya and Isono, Masato and Justesen, Johanne M and Katsuya, Tomohiro and Kibriya, Muhammad G and Kim, Young Jin and Kishimoto, Miyako and Koh, Woon-Puay and Kohara, Katsuhiko and Kumari, Meena and Kwek, Kenneth and Lee, Nanette R and Lee, Jeannette and Liao, Jiemin and Lieb, Wolfgang and Liewald, David C M and Matsubara, Tatsuaki and Matsushita, Yumi and Meitinger, Thomas and Mihailov, Evelin and Milani, Lili and Mills, Rebecca and Mononen, Nina and Müller-Nurasyid, Martina and Nabika, Toru and Nakashima, Eitaro and Ng, Hong Kiat and Nikus, Kjell and Nutile, Teresa and Ohkubo, Takayoshi and Ohnaka, Keizo and Parish, Sarah and Paternoster, Lavinia and Peng, Hao and Peters, Annette and Pham, Son T and Pinidiyapathirage, Mohitha J and Rahman, Mahfuzar and Rakugi, Hiromi and Rolandsson, Olov and Rozario, Michelle Ann and Ruggiero, Daniela and Sala, Cinzia F and Sarju, Ralhan and Shimokawa, Kazuro and Snieder, Harold and Sparsø, Thomas and Spiering, Wilko and Starr, John M and Stott, David J and Stram, Daniel O and Sugiyama, Takao and Szymczak, Silke and Tang, W H Wilson and Tong, Lin and Trompet, Stella and Turjanmaa, Väinö and Ueshima, Hirotsugu and Uitterlinden, André G and Umemura, Satoshi and Vaarasmaki, Marja and van Dam, Rob M and van Gilst, Wiek H and van Veldhuisen, Dirk J and Viikari, Jorma S and Waldenberger, Melanie and Wang, Yiqin and Wang, Aili and Wilson, Rory and Wong, Tien-Yin and Xiang, Yong-Bing and Yamaguchi, Shuhei and Ye, Xingwang and Young, Robin D and Young, Terri L and Yuan, Jian-Min and Zhou, Xueya and Asselbergs, Folkert W and Ciullo, Marina and Clarke, Robert and Deloukas, Panos and Franke, Andre and Franks, Paul and Franks, Steve and Friedlander, Yechiel and Gross, Myron D and Guo, Zhirong and Hansen, Torben and Jarvelin, Marjo-Riitta and Jørgensen, Torben and Jukema, J Wouter and Kähönen, Mika and Kajio, Hiroshi and Kivimaki, Mika and Lee, Jong-Young and Lehtimäki, Terho and Linneberg, Allan and Miki, Tetsuro and Pedersen, Oluf and Samani, Nilesh J and Sørensen, Thorkild I A and Takayanagi, Ryoichi and Toniolo, Daniela and Ahsan, Habibul and Allayee, Hooman and Chen, Yuan-Tsong and Danesh, John and Deary, Ian J and Franco, Oscar H and Franke, Lude and Heijman, Bastiaan T and Holbrook, Joanna D and Isaacs, Aaron and Kim, Bong-Jo and Lin, Xu and Liu, Jianjun and März, Winfried and Metspalu, Andres and Mohlke, Karen L and Sanghera, Dharambir K and Shu, Xiao-Ou and van Meurs, Joyce B J and Vithana, Eranga and Wickremasinghe, Ananda R and Wijmenga, Cisca and Wolffenbuttel, Bruce H W and Yokota, Mitsuhiro and Zheng, Wei and Zhu, Dingliang and Vineis, Paolo and Kyrtopoulos, Soterios A and Kleinjans, Jos C S and McCarthy, Mark I and Soong, Richie and Gieger, Christian and Scott, James and Teo, Yik-Ying and He, Jiang and Elliott, Paul and Tai, E Shyong and van der Harst, Pim and Kooner, Jaspal S and Chambers, John C},
  issn         = {1546-1718},
  language     = {eng},
  number       = {11},
  pages        = {93--1282},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.},
  url          = {http://dx.doi.org/10.1038/ng.3405},
  volume       = {47},
  year         = {2015},
}