Abstract
Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140mmg Hg systolic blood pressure ≥90mmg Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3 GUCY1B3, NPR3 C5orf23, ADM, FURIN FES, GOSR2, GNAS EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
Original language | English |
---|---|
Pages (from-to) | 103-109 |
Number of pages | 7 |
Journal | Nature |
Volume | 478 |
Issue number | 7367 |
DOIs | |
State | Published - Oct 6 2011 |
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In: Nature, Vol. 478, No. 7367, 06.10.2011, p. 103-109.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk
AU - Ehret, Georg B.
AU - Munroe, Patricia B.
AU - Rice, Kenneth M.
AU - Bochud, Murielle
AU - Johnson, Andrew D.
AU - Chasman, Daniel I.
AU - Smith, Albert V.
AU - Tobin, Martin D.
AU - Verwoert, Germaine C.
AU - Hwang, Shih Jen
AU - Pihur, Vasyl
AU - Vollenweider, Peter
AU - O'Reilly, Paul F.
AU - Amin, Najaf
AU - Bragg-Gresham, Jennifer L.
AU - Teumer, Alexander
AU - Glazer, Nicole L.
AU - Launer, Lenore
AU - Zhao, Jing Hua
AU - Aulchenko, Yurii
AU - Heath, Simon
AU - Sober, Siim
AU - Parsa, Afshin
AU - Luan, Jian'an
AU - Arora, Pankaj
AU - Dehghan, Abbas
AU - Zhang, Feng
AU - Lucas, Gavin
AU - Hicks, Andrew A.
AU - Jackson, Anne U.
AU - Peden, John F.
AU - Tanaka, Toshiko
AU - Wild, Sarah H.
AU - Rudan, Igor
AU - Igl, Wilmar
AU - Milaneschi, Yuri
AU - Parker, Alex N.
AU - Fava, Cristiano
AU - Chambers, John C.
AU - Fox, Ervin R.
AU - Kumari, Meena
AU - Go, Min Jin
AU - van der Harst, Pim
AU - Kao, Wen Hong Linda
AU - Sjögren, Marketa
AU - Vinay, D. G.
AU - Alexander, Myriam
AU - Tabara, Yasuharu
AU - Shaw-Hawkins, Sue
AU - Whincup, Peter H.
AU - Liu, Yongmei
AU - Shi, Gang
AU - Kuusisto, Johanna
AU - Tayo, Bamidele
AU - Seielstad, Mark
AU - Sim, Xueling
AU - Hoang Nguyen, Khanh Dung
AU - Lehtimäki, Terho
AU - Matullo, Giuseppe
AU - Wu, Ying
AU - Gaunt, Tom R.
AU - Charlotte Onland-Moret, N.
AU - Cooper, Matthew N.
AU - Platou, Carl G.P.
AU - Org, Elin
AU - Hardy, Rebecca
AU - Dahgam, Santosh
AU - Palmen, Jutta
AU - Vitart, Veronique
AU - Braund, Peter S.
AU - Kuznetsova, Tatiana
AU - Uiterwaal, Cuno S.P.M.
AU - Adeyemo, Adebowale
AU - Palmas, Walter
AU - Campbell, Harry
AU - Ludwig, Barbara
AU - Tomaszewski, Maciej
AU - Tzoulaki, Ioanna
AU - Palmer, Nicholette D.
AU - Aspelund, Thor
AU - Garcia, Melissa
AU - Chang, Yen Pei C.
AU - O'Connell, Jeffrey R.
AU - Steinle, Nanette I.
AU - Grobbee, Diederick E.
AU - Arking, Dan E.
AU - Kardia, Sharon L.
AU - Morrison, Alanna C.
AU - Hernandez, Dena
AU - Najjar, Samer
AU - McArdle, Wendy L.
AU - Hadley, David
AU - Brown, Morris J.
AU - Connell, John M.
AU - Hingorani, Aroon D.
AU - Day, Ian N.M.
AU - Lawlor, Debbie A.
AU - Beilby, John P.
AU - Lawrence, Robert W.
AU - Clarke, Robert
AU - Hopewell, Jemma C.
AU - Ongen, Halit
AU - Dreisbach, Albert W.
AU - Li, Yali
AU - Hunter Young, J.
AU - Bis, Joshua C.
AU - Kähönen, Mika
AU - Viikari, Jorma
AU - Adair, Linda S.
AU - Lee, Nanette R.
AU - Chen, Ming Huei
AU - Olden, Matthias
AU - Pattaro, Cristian
AU - Bolton, Judith A.Hoffman
AU - Köttgen, Anna
AU - Bergmann, Sven
AU - Mooser, Vincent
AU - Chaturvedi, Nish
AU - Frayling, Timothy M.
AU - Islam, Muhammad
AU - Jafar, Tazeen H.
AU - Erdmann, Jeanette
AU - Kulkarni, Smita R.
AU - Bornstein, Stefan R.
AU - Grässler, Jürgen
AU - Groop, Leif
AU - Voight, Benjamin F.
AU - Kettunen, Johannes
AU - Howard, Philip
AU - Taylor, Andrew
AU - Guarrera, Simonetta
AU - Ricceri, Fulvio
AU - Emilsson, Valur
AU - Plump, Andrew
AU - Barroso, Inês
AU - Khaw, Kay Tee
AU - Weder, Alan B.
AU - Hunt, Steven C.
AU - Sun, Yan V.
AU - Bergman, Richard N.
AU - Collins, Francis S.
AU - Bonnycastle, Lori L.
AU - Scott, Laura J.
AU - Stringham, Heather M.
AU - Peltonen, Leena
AU - Perola, Markus
AU - Vartiainen, Erkki
AU - Brand, Stefan Martin
AU - Staessen, Jan A.
AU - Wang, Thomas J.
AU - Burton, Paul R.
AU - Artigas, Maria Soler
AU - Dong, Yanbin
AU - Snieder, Harold
AU - Wang, Xiaoling
AU - Zhu, Haidong
AU - Lohman, Kurt K.
AU - Rudock, Megan E.
AU - Heckbert, Susan R.
AU - Smith, Nicholas L.
AU - Wiggins, Kerri L.
AU - Doumatey, Ayo
AU - Shriner, Daniel
AU - Veldre, Gudrun
AU - Viigimaa, Margus
AU - Kinra, Sanjay
AU - Prabhakaran, Dorairaj
AU - Tripathy, Vikal
AU - Langefeld, Carl D.
AU - Rosengren, Annika
AU - Thelle, Dag S.
AU - Corsi, Anna Maria
AU - Singleton, Andrew
AU - Forrester, Terrence
AU - Hilton, Gina
AU - McKenzie, Colin A.
AU - Salako, Tunde
AU - Iwai, Naoharu
AU - Kita, Yoshikuni
AU - Ogihara, Toshio
AU - Ohkubo, Takayoshi
AU - Okamura, Tomonori
AU - Ueshima, Hirotsugu
AU - Umemura, Satoshi
AU - Eyheramendy, Susana
AU - Meitinger, Thomas
AU - Wichmann, H. Erich
AU - Cho, Yoon Shin
AU - Kim, Hyung Lae
AU - Lee, Jong Young
AU - Scott, James
AU - Sehmi, Joban S.
AU - Zhang, Weihua
AU - Hedblad, Bo
AU - Nilsson, Peter
AU - Smith, George Davey
AU - Wong, Andrew
AU - Narisu, Narisu
AU - Stančáková, Alena
AU - Raffel, Leslie J.
AU - Yao, Jie
AU - Kathiresan, Sekar
AU - O'Donnell, Christopher J.
AU - Schwartz, Stephen M.
AU - Arfan Ikram, M.
AU - Longstreth, W. T.
AU - Mosley, Thomas H.
AU - Seshadri, Sudha
AU - Shrine, Nick R.G.
AU - Wain, Louise V.
AU - Morken, Mario A.
AU - Swift, Amy J.
AU - Laitinen, Jaana
AU - Prokopenko, Inga
AU - Zitting, Paavo
AU - Cooper, Jackie A.
AU - Humphries, Steve E.
AU - Danesh, John
AU - Rasheed, Asif
AU - Goel, Anuj
AU - Hamsten, Anders
AU - Watkins, Hugh
AU - Bakker, Stephan J.L.
AU - van Gilst, Wiek H.
AU - Janipalli, Charles S.
AU - Radha Mani, K.
AU - Yajnik, Chittaranjan S.
AU - Hofman, Albert
AU - Mattace-Raso, Francesco U.S.
AU - Oostra, Ben A.
AU - Demirkan, Ayse
AU - Isaacs, Aaron
AU - Rivadeneira, Fernando
AU - Lakatta, Edward G.
AU - Orru, Marco
AU - Scuteri, Angelo
AU - Ala-Korpela, Mika
AU - Kangas, Antti J.
AU - Lyytikäinen, Leo Pekka
AU - Soininen, Pasi
AU - Tukiainen, Taru
AU - Würtz, Peter
AU - Twee-HeeOng, Rick
AU - Dörr, Marcus
AU - Kroemer, Heyo K.
AU - Völker, Uwe
AU - Völzke, Henry
AU - Galan, Pilar
AU - Hercberg, Serge
AU - Lathrop, Mark
AU - Zelenika, Diana
AU - Deloukas, Panos
AU - Mangino, Massimo
AU - Spector, Tim D.
AU - Zhai, Guangju
AU - Meschia, James F.
AU - Nalls, Michael A.
AU - Sharma, Pankaj
AU - Terzic, Janos
AU - Kranthi Kumar, M. V.
AU - Denniff, Matthew
AU - Zukowska-Szczechowska, Ewa
AU - Wagenknecht, Lynne E.
AU - Fowkes, F. Gerald R.
AU - Charchar, Fadi J.
AU - Schwarz, Peter E.H.
AU - Hayward, Caroline
AU - Guo, Xiuqing
AU - Rotimi, Charles
AU - Bots, Michiel L.
AU - Brand, Eva
AU - Samani, Nilesh J.
AU - Polasek, Ozren
AU - Talmud, Philippa J.
AU - Nyberg, Fredrik
AU - Kuh, Diana
AU - Laan, Maris
AU - Hveem, Kristian
AU - Palmer, Lyle J.
AU - van der Schouw, Yvonne T.
AU - Casas, Juan P.
AU - Mohlke, Karen L.
AU - Vineis, Paolo
AU - Raitakari, Olli
AU - Ganesh, Santhi K.
AU - Wong, Tien Y.
AU - Shyong Tai, E.
AU - Cooper, Richard S.
AU - Laakso, Markku
AU - Rao, Dabeeru C.
AU - Harris, Tamara B.
AU - Morris, Richard W.
AU - Dominiczak, Anna F.
AU - Kivimaki, Mika
AU - Marmot, Michael G.
AU - Miki, Tetsuro
AU - Saleheen, Danish
AU - Chandak, Giriraj R.
AU - Coresh, Josef
AU - Navis, Gerjan
AU - Salomaa, Veikko
AU - Han, Bok Ghee
AU - Zhu, Xiaofeng
AU - Kooner, Jaspal S.
AU - Melander, Olle
AU - Ridker, Paul M.
AU - Bandinelli, Stefania
AU - Gyllensten, Ulf B.
AU - Wright, Alan F.
AU - Wilson, James F.
AU - Ferrucci, Luigi
AU - Farrall, Martin
AU - Tuomilehto, Jaakko
AU - Pramstaller, Peter P.
AU - Elosua, Roberto
AU - Soranzo, Nicole
AU - Sijbrands, Eric J.G.
AU - Altshuler, David
AU - Loos, Ruth J.F.
AU - Shuldiner, Alan R.
AU - Gieger, Christian
AU - Meneton, Pierre
AU - Uitterlinden, Andre G.
AU - Wareham, Nicholas J.
AU - Gudnason, Vilmundur
AU - Rotter, Jerome I.
AU - Rettig, Rainer
AU - Uda, Manuela
AU - Strachan, David P.
AU - Witteman, Jacqueline C.M.
AU - Hartikainen, Anna Liisa
AU - Beckmann, Jacques S.
AU - Boerwinkle, Eric
AU - Vasan, Ramachandran S.
AU - Boehnke, Michael
AU - Larson, Martin G.
AU - Järvelin, Marjo Riitta
AU - Psaty, Bruce M.
AU - Abecasis, Gonçalo R.
AU - Chakravarti, Aravinda
AU - Elliott, Paul
AU - van Duijn, Cornelia M.
AU - Newton-Cheh, Christopher
AU - Levy, Daniel
AU - Caulfield, Mark J.
AU - Johnson, Toby
N1 - Funding Information: 47Centre for Cellular and Molecular Biology (CCMB), Council of Scientific and Industrial Research (CSIR), Uppal Road, Hyderabad 500 007, India. 48Department of Public Health andPrimaryCare,UniversityofCambridge,CB18RN,UK.49DepartmentofBasicMedical Research and Education, and Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon, 791-0295, Japan. 50Division of Community Health Sciences, St George’s University of London, London SW17 0RE, UK. 51Epidemiology & Prevention,Division ofPublic Health Sciences, Wake Forest University Schoolof Medicine, Winston-Salem,NorthCarolina27157,USA.52DivisionofBiostatisticsandDepartmentof Genetics, School of Medicine, Washington University in St. Louis, Saint Louis, Missouri 63110, USA. 53Department of Medicine, University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland. 54Department of Preventive Medicine and Epidemiology, Loyola University Medical School, Maywood, Illinois 60153, USA. 55Department of Laboratory Medicine & Institute of Human Genetics, University of California San Francisco, 513 Parnassus Ave. San Francisco, California 94143, USA. 56Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore138672,Singapore.57CentreforMolecularEpidemiology,YongLooLinSchool of Medicine, National University of Singapore, Singapore 117597, Singapore. 58Department of Clinical Chemistry, University of Tampere and Tampere University Hospital, Tampere 33521, Finland. 59Department of Genetics, Biology and Biochemistry, University of Torino, Via Santena 19, 10126 Torino, Italy. 60Human Genetics Foundation (HUGEF), Via Nizza 52, 10126 Torino, Italy. 61Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA. 62MRC Centre for Causal Analyses in TranslationalEpidemiology, School ofSocial& Community Medicine,University ofBristol, Bristol BS8 2BN, UK. 63Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands.
PY - 2011/10/6
Y1 - 2011/10/6
N2 - Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140mmg Hg systolic blood pressure ≥90mmg Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3 GUCY1B3, NPR3 C5orf23, ADM, FURIN FES, GOSR2, GNAS EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
AB - Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140mmg Hg systolic blood pressure ≥90mmg Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3 GUCY1B3, NPR3 C5orf23, ADM, FURIN FES, GOSR2, GNAS EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
UR - http://www.scopus.com/inward/record.url?scp=80053907554&partnerID=8YFLogxK
U2 - 10.1038/nature10405
DO - 10.1038/nature10405
M3 - Article
C2 - 21909115
AN - SCOPUS:80053907554
SN - 0028-0836
VL - 478
SP - 103
EP - 109
JO - Nature
JF - Nature
IS - 7367
ER -