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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-11

AUTHORS

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, Tarunveer S 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, Yi Zhang, Imke Aits, Alexessander Da Silva Couto Alves, Shikta Das, Rajkumar Dorajoo, Jemma C Hopewell, Yun Kyoung Kim, Robert W Koivula, Jian'an Luan, Leo-Pekka Lyytikäinen, Quang N Nguyen, Mark A Pereira, Iris Postmus, Olli T Raitakari, Molly Scannell Bryan, Robert A Scott, Rossella Sorice, Vinicius Tragante, Michela Traglia, Jon White, Ken Yamamoto, Yonghong Zhang, Linda S Adair, Alauddin Ahmed, Koichi Akiyama, Rasheed Asif, Tin Aung, Inês Barroso, Andrew Bjonnes, Timothy R Braun, Hui Cai, Li-Ching Chang, Chien-Hsiun Chen, Ching-Yu Cheng, Yap-Seng Chong, Rory Collins, Regina Courtney, Gail Davies, Graciela Delgado, Loi D, Pieter A Doevendans, Ron T Gansevoort, Yu-Tang Gao, Tanja B Grammer, Niels Grarup, Jagvir Grewal, Dongfeng Gu, Gurpreet S Wander, Anna-Liisa Hartikainen, Stanley L Hazen, Jing He, Chew-Kiat Heng, James E Hixson, Albert Hofman, Chris Hsu, Wei Huang, Lise L N Husemoen, Joo-Yeon Hwang, Sahoko Ichihara, Michiya Igase, Masato Isono, Johanne M Justesen, Tomohiro Katsuya, Muhammad G Kibriya, Young Jin Kim, Miyako Kishimoto, Woon-Puay Koh, Katsuhiko Kohara, Meena Kumari, Kenneth Kwek, Nanette R Lee, Jeannette Lee, Jiemin Liao, Wolfgang Lieb, David C M Liewald, Tatsuaki Matsubara, Yumi Matsushita, Thomas Meitinger, Evelin Mihailov, Lili Milani, Rebecca Mills, Nina Mononen, Martina Müller-Nurasyid, Toru Nabika, Eitaro Nakashima, Hong Kiat Ng, Kjell Nikus, Teresa Nutile, Takayoshi Ohkubo, Keizo Ohnaka, Sarah Parish, Lavinia Paternoster, Hao Peng, Annette Peters, Son T Pham, Mohitha J Pinidiyapathirage, Mahfuzar Rahman, Hiromi Rakugi, Olov Rolandsson, Michelle Ann Rozario, Daniela Ruggiero, Cinzia F Sala, Ralhan Sarju, Kazuro Shimokawa, Harold Snieder, Thomas Sparsø, Wilko Spiering, John M Starr, David J Stott, Daniel O Stram, Takao Sugiyama, Silke Szymczak, W H Wilson Tang, Lin Tong, Stella Trompet, Väinö Turjanmaa, Hirotsugu Ueshima, André G Uitterlinden, Satoshi Umemura, Marja Vaarasmaki, Rob M van Dam, Wiek H van Gilst, Dirk J van Veldhuisen, Jorma S Viikari, Melanie Waldenberger, Yiqin Wang, Aili Wang, Rory Wilson, Tien-Yin Wong, Yong-Bing Xiang, Shuhei Yamaguchi, Xingwang Ye, Robin D Young, Terri L Young, Jian-Min Yuan, Xueya Zhou, Folkert W Asselbergs, Marina Ciullo, Robert Clarke, Panos Deloukas, Andre Franke, Paul W Franks, Steve Franks, Yechiel Friedlander, Myron D Gross, Zhirong Guo, Torben Hansen, Marjo-Riitta Jarvelin, Torben Jørgensen, J Wouter Jukema, Mika Kähönen, Hiroshi Kajio, Mika Kivimaki, Jong-Young Lee, Terho Lehtimäki, Allan Linneberg, Tetsuro Miki, Oluf Pedersen, Nilesh J Samani, Thorkild I A Sørensen, Ryoichi Takayanagi, Daniela Toniolo, BIOS-consortium, CAIo GRAMplusCD, LifeLines Cohort Study, The InterAct Consortium, Habibul Ahsan, Hooman Allayee, Yuan-Tsong Chen, John Danesh, Ian J Deary, Oscar H Franco, Lude Franke, Bastiaan T Heijman, Joanna D Holbrook, Aaron Isaacs, Bong-Jo Kim, Xu Lin, Jianjun Liu, Winfried März, Andres Metspalu, Karen L Mohlke, Dharambir K Sanghera, Xiao-Ou Shu, Joyce B J van Meurs, Eranga Vithana, Ananda R Wickremasinghe, Cisca Wijmenga, Bruce H W Wolffenbuttel, Mitsuhiro Yokota, Wei Zheng, Dingliang Zhu, Paolo Vineis, Soterios A Kyrtopoulos, Jos C S Kleinjans, Mark I McCarthy, Richie Soong, Christian Gieger, James Scott, Yik-Ying Teo, Jiang He, Paul Elliott, E Shyong Tai, Pim van der Harst, Jaspal S Kooner, John C Chambers

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. More... »

PAGES

1282-1293

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    11

    VOLUME

    47

    Author Affiliations

  • National Center For Global Health and Medicine
  • Agency for Science, Technology and Research
  • University Medical Center Groningen
  • Ealing Hospital
  • Tulane University
  • University of Pennsylvania
  • Imperial College London
  • Wellcome Centre for Human Genetics
  • German Center for Diabetes Research
  • Steno Diabetes Center
  • Erasmus University Medical Center
  • Vanderbilt University
  • Broad Institute
  • Korea National Institute of Health
  • University of Edinburgh
  • University of Southern California
  • University of Tartu
  • University of Kelaniya
  • National University of Singapore
  • Heidelberg University
  • Shanghai Institutes for Biological Sciences
  • Nagoya University Hospital
  • University of Ottawa
  • Kyoto University
  • Singapore Institute for Clinical Sciences
  • University of North Carolina at Chapel Hill
  • China Medical University
  • Shanghai Institute of Hypertension
  • Kiel University
  • Genome Institute of Singapore
  • University of Oxford
  • Skåne University Hospital
  • Institute of Metabolic Science
  • University of Tampere
  • Bạch Mai Hospital
  • University of Minnesota
  • Netherlands Consortium for Healthy Ageing
  • University of Turku
  • National Research Council
  • University Medical Center Utrecht
  • IRCCS Materno Infantile Burlo Garofolo
  • University College London
  • Kyushu University
  • Soochow University
  • University of North Carolina System
  • University of Chicago Research Bangladesh
  • Center for Non-Communicable Diseases
  • Singapore National Eye Center
  • University of Oklahoma Health Sciences Center
  • Institute of Biomedical Sciences, Academia Sinica
  • Duke NUS Graduate Medical School
  • Shanghai Cancer Institute
  • University of Copenhagen
  • Peking Union Medical College Hospital
  • Dayanand Medical College & Hospital
  • Oulu University Hospital
  • Cleveland Clinic
  • The University of Texas Health Science Center at Houston
  • Rigshospitalet
  • Mie University
  • Ehime University
  • Osaka University
  • KK Women's and Children's Hospital
  • University of San Carlos
  • Aichi Gakuin University
  • Technical University Munich
  • German Centre for Cardiovascular Research
  • Shimane University
  • Chubu Rosai Hospital
  • Teikyo University
  • University of Bristol
  • Umeå University
  • San Raffaele Hospital
  • University of Glasgow
  • Institute for Adult Diseases Asahi Life Foundation
  • Leiden University Medical Center
  • Shiga University of Medical Science
  • Yokohama City University
  • University of Cambridge
  • Duke University
  • University of Pittsburgh Cancer Institute
  • University of Hong Kong
  • King Abdulaziz University
  • Harvard University
  • Hebrew University of Jerusalem
  • University of Oulu
  • Ministry of Health and Welfare
  • Glenfield Hospital
  • Istituto di Genetica Molecolare
  • Wellcome Sanger Institute
  • Synlab (Germany)
  • National Hellenic Research Foundation
  • Maastricht University
  • Oxford Centre for Diabetes, Endocrinology and Metabolism
  • Imperial College Healthcare NHS Trust
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3405

    DOI

    http://dx.doi.org/10.1038/ng.3405

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1012851637

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26390057


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