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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Surendran, Praveen (author)
University of Cambridge
Feofanova, Elena V. (author)
Lahrouchi, Najim (author)
show more...
Ntalla, Ioanna (author)
Karthikeyan, Savita (author)
Cook, James (author)
Chen, Lingyan (author)
Mifsud, Borbala (author)
Yao, Chen (author)
Tuomi, Tiinamaija (author)
Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups,University of Helsinki
Cartwright, James H. (author)
Hellwege, Jacklyn N. (author)
Giri, Ayush (author)
Tragante, Vinicius (author)
Thorleifsson, Gudmar (author)
Liu, Dajiang J. (author)
Prins, Bram P. (author)
Stewart, Isobel D. (author)
Cabrera, Claudia P. (author)
Eales, James M. (author)
Akbarov, Artur (author)
Auer, Paul L. (author)
Bielak, Lawrence F. (author)
Bis, Joshua C. (author)
Braithwaite, Vickie S. (author)
Brody, Jennifer A. (author)
Daw, E. Warwick (author)
Warren, Helen R. (author)
Drenos, Fotios (author)
Nielsen, Sune Fallgaard (author)
Faul, Jessica D. (author)
Fauman, Eric B. (author)
Fava, Cristiano (author)
Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
Ferreira, Teresa (author)
Foley, Christopher N. (author)
Franceschini, Nora (author)
Gao, He (author)
Giannakopoulou, Olga (author)
Giulianini, Franco (author)
Gudbjartsson, Daniel F. (author)
Guo, Xiuqing (author)
Harris, Sarah E. (author)
Havulinna, Aki S. (author)
Helgadottir, Anna (author)
Huffman, Jennifer E. (author)
Hwang, Shih-Jen (author)
Kanoni, Stavroula (author)
Kontto, Jukka (author)
Larson, Martin G. (author)
Li-Gao, Ruifang (author)
Lindstrom, Jaana (author)
Lotta, Luca A. (author)
Lu, Yingchang (author)
Luan, Jian'an (author)
Mahajan, Anubha (author)
Malerba, Giovanni (author)
Masca, Nicholas G. D. (author)
Mei, Hao (author)
Menni, Cristina (author)
Mook-Kanamori, Dennis O. (author)
Mosen-Ansorena, David (author)
Muller-Nurasyid, Martina (author)
Pare, Guillaume (author)
Paul, Dirk S. (author)
Perola, Markus (author)
Poveda, Alaitz (author)
Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
Rauramaa, Rainer (author)
Richard, Melissa (author)
Richardson, Tom G. (author)
Sepulveda, Nuno (author)
Sim, Xueling (author)
Smith, Albert, V (author)
Smith, Jennifer A. (author)
Staley, James R. (author)
Stanakova, Alena (author)
Sulem, Patrick (author)
Theriault, Sebastien (author)
Thorsteinsdottir, Unnur (author)
Trompet, Stella (author)
V. Varga, Tibor (author)
Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
Edwards, Digna R. Velez (author)
Veronesi, Giovanni (author)
Weiss, Stefan (author)
Willems, Sara M. (author)
Yao, Jie (author)
Young, Robin (author)
Yu, Bing (author)
Zhang, Weihua (author)
Zhao, Jing-Hua (author)
Zhao, Wei (author)
Evangelou, Evangelos (author)
Aeschbacher, Stefanie (author)
Asllanaj, Eralda (author)
Blankenberg, Stefan (author)
Bonnycastle, Lori L. (author)
Bork-Jensen, Jette (author)
Brandslund, Ivan (author)
Braund, Peter S. (author)
Burgess, Stephen (author)
Cho, Kelly (author)
Christensen, Cramer (author)
Connell, John (author)
de Mutsert, Renee (author)
Dominiczak, Anna F. (author)
Dorr, Marcus (author)
Eiriksdottir, Gudny (author)
Farmaki, Aliki-Eleni (author)
Gaziano, J. Michael (author)
Grarup, Niels (author)
Groop, Leif (author)
Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,University of Helsinki
Hallmans, Göran, 1947- (author)
Umeå universitet,Näringsforskning
Hansen, Torben (author)
Have, Christian T. (author)
Heiss, Gerardo (author)
Jorgensen, Marit E. (author)
Jousilahti, Pekka (author)
Kajantie, Eero (author)
Kamat, Mihir (author)
Karajamaki, AnneMari (author)
Karpe, Fredrik (author)
Koistinen, Heikki A. (author)
Kovesdy, Csaba P. (author)
Kuulasmaa, Kari (author)
Laatikainen, Tiina (author)
Lannfelt, Lars (author)
Lee, I-Te (author)
Lee, Wen-Jane (author)
Linneberg, Allan (author)
Martin, Lisa W. (author)
Moitry, Marie (author)
University of Cambridge,Novo Nordisk Research Centre Oxford
Nadkarni, Girish (author)
Neville, Matt J. (author)
Palmer, Colin N. A. (author)
Papanicolaou, George J. (author)
Pedersen, Oluf (author)
Peters, James (author)
Poulter, Neil (author)
Rasheed, Asif (author)
Rasmussen, Katrine L. (author)
Rayner, N. William (author)
Magi, Reedik (author)
Renström, Frida (author)
Lund University,Lunds universitet,Umeå universitet,Näringsforskning,Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital Malmö, Sweden,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
Rettig, Rainer (author)
Rossouw, Jacques (author)
Schreiner, Pamela J. (author)
Sever, Peter S. (author)
Sigurdsson, Emil L. (author)
Skaaby, Tea (author)
Sun, Yan, V (author)
Sundström, Johan, Professor, 1971- (author)
Uppsala universitet,Institutionen för medicinska vetenskaper
Thorgeirsson, Gudmundur (author)
Esko, Tonu (author)
Trabetti, Elisabetta (author)
Tsao, Philip S. (author)
Tuomi, Tiinamaija (author)
Turner, Stephen T. (author)
Tzoulaki, Ioanna (author)
Vaartjes, Ilonca (author)
Vergnaud, Anne-Claire (author)
Willer, Cristen J. (author)
Wilson, Peter W. F. (author)
Witte, Daniel R. (author)
Yonova-Doing, Ekaterina (author)
Zhang, He (author)
Aliya, Naheed (author)
Almgren, Peter (author)
Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Kardiovaskulär forskning - hypertoni,Diabetes - Cardiovascular Disease,Lund University Research Groups,Cardiovascular Research - Hypertension
Amouyel, Philippe (author)
Asselbergs, Folkert W. (author)
Barnes, Michael R. (author)
Blakemore, Alexandra, I (author)
Boehnke, Michael (author)
Bots, Michiel L. (author)
Bottinger, Erwin P. (author)
Buring, Julie E. (author)
Chambers, John C. (author)
Chen, Yii-Der Ida (author)
Chowdhury, Rajiv (author)
Conen, David (author)
Correa, Adolfo (author)
Smith, George Davey (author)
de Boer, Rudolf A. (author)
Deary, Ian J. (author)
Dedoussis, George (author)
Deloukas, Panos (author)
Di Angelantonio, Emanuele (author)
Elliott, Paul (author)
Felix, Stephan B. (author)
Ferrieres, Jean (author)
Ford, Ian (author)
Fornage, Myriam (author)
Franks, Paul W. (author)
Umeå University,Lund University,Lunds universitet,Umeå universitet,Näringsforskning,Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital Malmö, Sweden; Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA; Oxford Center for Diabetes, Endocrinology & Metabolism, Radcliff Department of Medicine, University of Oxford, Oxford,UK,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
Franks, Stephen (author)
Frossard, Philippe (author)
Gambaro, Giovanni (author)
Gaunt, Tom R. (author)
Groop, Leif (author)
Gudnason, Vilmundur (author)
Harris, Tamara B. (author)
Hayward, Caroline (author)
Hennig, Branwen J. (author)
Herzig, Karl-Heinz (author)
Ingelsson, Erik (author)
Tuomilehto, Jaakko (author)
Jarvelin, Marjo-Riitta (author)
Jukema, J. Wouter (author)
Kardia, Sharon L. R. (author)
Kee, Frank (author)
Kooner, Jaspal S. (author)
Kooperberg, Charles (author)
Launer, Lenore J. (author)
Lind, Lars (author)
Loos, Ruth J. F. (author)
Majumder, Abdulla Al Shafi (author)
Laakso, Markku (author)
McCarthy, Mark, I (author)
Melander, Olle (author)
Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
Mohlke, Karen L. (author)
Murray, Alison D. (author)
Nordestgaard, Borge Gronne (author)
Orho-Melander, Marju (author)
Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups
Packard, Chris J. (author)
Padmanabhan, Sandosh (author)
Palmas, Walter (author)
Polasek, Ozren (author)
Porteous, David J. (author)
Prentice, Andrew M. (author)
Province, Michael A. (author)
Relton, Caroline L. (author)
Rice, Kenneth (author)
Ridker, Paul M. (author)
Rolandsson, Olov (author)
Umeå universitet,Näringsforskning
Rosendaal, Frits R. (author)
Rotter, Jerome, I (author)
Rudan, Igor (author)
Salomaa, Veikko (author)
Samani, Nilesh J. (author)
Sattar, Naveed (author)
Sheu, Wayne H-H (author)
Smith, Blair H. (author)
Soranzo, Nicole (author)
Spector, Timothy D. (author)
Starr, John M. (author)
Sebert, Sylvain (author)
Taylor, Kent D. (author)
Lakka, Timo A. (author)
Timpson, Nicholas J. (author)
Tobin, Martin D. (author)
van der Harst, Pim (author)
van der Meer, Peter (author)
Ramachandran, Vasan S. (author)
Verweij, Niek (author)
Virtamo, Jarmo (author)
Volker, Uwe (author)
Weir, David R. (author)
Zeggini, Eleftheria (author)
Charchar, Fadi J. (author)
Wareham, Nicholas J. (author)
Langenberg, Claudia (author)
Tomaszewski, Maciej (author)
Butterworth, Adam S. (author)
Caulfield, Mark J. (author)
Danesh, John (author)
Edwards, Todd L. (author)
Holm, Hilma (author)
Hung, Adriana M. (author)
Lindgren, Cecilia M. (author)
Liu, Chunyu (author)
Manning, Alisa K. (author)
Morris, Andrew P. (author)
Morrison, Alanna C. (author)
O'Donnell, Christopher J. (author)
Psaty, Bruce M. (author)
Saleheen, Danish (author)
Stefansson, Kari (author)
Boerwinkle, Eric (author)
Chasman, Daniel, I (author)
Levy, Daniel (author)
Newton-Cheh, Christopher (author)
Munroe, Patricia B. (author)
Howson, Joanna M. M. (author)
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 (creator_code:org_t)
et al 
2020-11-23
2020
English.
In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

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About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
and Medical Genetics
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
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Nature Genetics
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Umeå University
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Uppsala University

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