Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Research output: Contribution to journalArticleScientificpeer-review

Researchers

  • Georg B. Ehret
  • Patricia B. Munroe
  • Kenneth M. Rice
  • Murielle Bochud
  • Andrew D. Johnson
  • Daniel I. Chasman
  • Albert Vernon Smith
  • Martin D. Tobin
  • Germaine C. Verwoert
  • Shih Jen Hwang
  • Vasyl Pihur
  • Peter Vollenweider
  • Paul F. O'reilly
  • Najaf Amin
  • Jennifer L. Bragg-Gresham
  • Alexander Teumer
  • Nicole L. Glazer
  • Lenore Launer
  • Jing Hua Zhao
  • Yurii S. Aulchenko
  • And 326 others
  • Simon Heath
  • Siim Sober
  • Afshin Parsa
  • Jian'an Luan
  • Pankaj Arora
  • Abbas Dehghan
  • Feng Zhang
  • Gavin Lucas
  • Andrew A. Hicks
  • Anne U. Jackson
  • John F. Peden
  • Toshiko Tanaka
  • Sarah H. Wild
  • Igor Rudan
  • Wilmar Igl
  • Yuri Milaneschi
  • Alex N. Parker
  • Cristiano Fava
  • John C. Chambers
  • Ervin R. Fox
  • Meena Kumari
  • Min Jin Go
  • Pim Van der Harst
  • Wen Hong Linda Kao
  • Marketa Sjögren
  • D. G. Vinay
  • Myriam Alexander
  • Yasuharu Tabara
  • Sue Shaw-Hawkins
  • Peter H. Whincup
  • Yongmei Liu
  • Gang Shi
  • Johanna Kuusisto
  • Bamidele O. Tayo
  • Mark Seielstad
  • Xueling Sim
  • Khanh Dung Hoang Nguyen
  • Terho Lehtimäki
  • Giuseppe Matullo
  • Ying Wu
  • Tom R. Gaunt
  • N. Charlotte Onland-Moret
  • Matthew N. Cooper
  • Carl G.P. Platou
  • Elin Org
  • Rebecca Hardy
  • Santosh Dahgam
  • Jutta Palmen
  • Veronique Vitart
  • Peter S. Braund
  • Tatiana Kuznetsova
  • Cuno S.P.M. Uiterwaal
  • Adebowale Adeyemo
  • Walter Palmas
  • Harry Campbell
  • Barbara Ludwig
  • Maciej Tomaszewski
  • Ioanna Tzoulaki
  • Nicholette D. Palmer
  • Thor Aspelund
  • Melissa E. Garcia
  • Yen Pei C. Chang
  • Jeffrey R. O'Connell
  • Nanette I. Steinle
  • Diederick E. Grobbee
  • Dan E. Arking
  • Sharon L. Kardia
  • Alanna C. Morrison
  • Dena Hernandez
  • Samer Najjar
  • Wendy L. McArdle
  • David Hadley
  • Morris J. Brown
  • John M. Connell
  • Aroon D. Hingorani
  • Ian N.M. Day
  • Debbie A. Lawlor
  • John P. Beilby
  • Robert W. Lawrence
  • Robert Clarke
  • Jemma C. Hopewell
  • Halit Ongen
  • Albert W. Dreisbach
  • Yali Li
  • J. Hunter Young
  • Joshua C. Bis
  • Mika Kähönen
  • Jorma Viikari
  • Linda S. Adair
  • Nanette R. Lee
  • Ming Huei Chen
  • Matthias Olden
  • Cristian Pattaro
  • Judith A.Hoffman Bolton
  • Anna Köttgen
  • Sven Bergmann
  • Vincent Mooser
  • Nish Chaturvedi
  • Timothy M. Frayling
  • Muhammad Islam
  • Tazeen H. Jafar
  • Jeanette Erdmann
  • Smita R. Kulkarni
  • Stefan R. Bornstein
  • Jürgen Grässler
  • Leif Groop
  • Benjamin F. Voight
  • Johannes Kettunen
  • Philip Howard
  • Andrew Taylor
  • Simonetta Guarrera
  • Fulvio Ricceri
  • Valur Emilsson
  • Andrew Plump
  • Inês Barroso
  • Kay Tee Khaw
  • Alan B. Weder
  • Steven C. Hunt
  • Yan V. Sun
  • Richard N. Bergman
  • Francis S. Collins
  • Lori L. Bonnycastle
  • Laura J. Scott
  • Heather M. Stringham
  • Leena Peltonen
  • Markus Perola
  • Erkki Vartiainen
  • Stefan Martin Brand
  • Jan A. Staessen
  • Thomas J. Wang
  • Paul R. Burton
  • Maria Soler Artigas
  • Yanbin Dong
  • Harold Snieder
  • Xiaoling Wang
  • Haidong Zhu
  • Kurt K. Lohman
  • Megan E. Rudock
  • Susan R. Heckbert
  • Nicholas L. Smith
  • Kerri L. Wiggins
  • Ayo Doumatey
  • Daniel Shriner
  • Gudrun Veldre
  • Margus Viigimaa
  • Sanjay Kinra
  • Dorairaj Prabhakaran
  • Vikal Tripathy
  • Carl D. Langefeld
  • Annika Rosengren
  • Dag S. Thelle
  • Anna Maria Corsi
  • Andrew Singleton
  • Terrence Forrester
  • Gina Hilton
  • Colin A. McKenzie
  • Tunde Salako
  • Naoharu Iwai
  • Yoshikuni Kita
  • Toshio Ogihara
  • Takayoshi Ohkubo
  • Tomonori Okamura
  • Hirotsugu Ueshima
  • Satoshi Umemura
  • Susana Eyheramendy
  • Thomas Meitinger
  • H. Erich Wichmann
  • Yoon Shin Cho
  • Hyung Lae Kim
  • Jong Young Lee
  • James P. Scott-Browne
  • Joban S. Sehmi
  • Weihua Zhang
  • Bo Hedblad
  • Peter Nilsson
  • George Davey Smith
  • Andrew Wong
  • Narisu Narisu
  • Alena Stančáková
  • Leslie J. Raffel
  • Jie Yao
  • Sekar Kathiresan
  • Christopher J. O'Donnell
  • Stephen M. Schwartz
  • M. Arfan Ikram
  • W. T. Longstreth
  • Thomas H. Mosley
  • Sudha Seshadri
  • Nick R.G. Shrine
  • Louise V. Wain
  • Mario A. Morken
  • Amy J. Swift
  • Jaana Laitinen
  • Inga Prokopenko
  • Paavo Zitting
  • Jackie A. Cooper
  • Steve E. Humphries
  • John Danesh
  • Asif Rasheed
  • Anuj Goel
  • Anders Hamsten
  • Hugh Watkins
  • Stephan J L Bakker
  • Wiek H. van Gilst
  • Charles S. Janipalli
  • K. Radha Mani
  • Chittaranjan S. Yajnik
  • Albert Hofman
  • Francesco U.S. Mattace-Raso
  • Ben A. Oostra
  • Ayse Demirkan
  • Aaron Isaacs
  • Fernando Rivadeneira
  • Edward G. Lakatta
  • Marco Orru
  • Angelo Scuteri
  • Mika Ala-Korpela
  • Antti J. Kangas
  • Leo-Pekka Lyytikäinen
  • Pasi Soininen
  • Taru Tukiainen
  • Peter Würtz
  • Rick Twee-HeeOng
  • Marcus Dörr
  • Heyo K. Kroemer
  • Uwe Völker
  • Henry Völzke
  • Pilar Galan
  • Serge Hercberg
  • Mark Lathrop
  • Diana Zelenika
  • Panos Deloukas
  • Massimo Mangino
  • Tim D. Spector
  • Guangju Zhai
  • James F. Meschia
  • Michael A. Nalls
  • Pankaj Sharma
  • Janos Terzic
  • M. V. Kranthi Kumar
  • Matthew Denniff
  • Ewa Zukowska-Szczechowska
  • Lynne E. Wagenknecht
  • F. Gerald R. Fowkes
  • Fadi J. Charchar
  • Peter E H Schwarz
  • Caroline Hayward
  • Xiuqing Guo
  • Charles Rotimi
  • Michiel L. Bots
  • Eva Brand
  • Nilesh J. Samani
  • Ozren Polasek
  • Philippa J. Talmud
  • Fredrik Nyberg
  • Diana Kuh
  • Maris Laan
  • Kristian Hveem
  • Lyle J. Palmer
  • Yvonne T. van der Schouw
  • Juan P. Casas
  • Karen L. Mohlke
  • Paolo Vineis
  • Olli Raitakari
  • Santhi K. Ganesh
  • Tien Y. Wong
  • E. Shyong Tai
  • Richard S. Cooper
  • Markku Laakso
  • Dabeeru C. Rao
  • Tamara B. Harris
  • Richard W. Morris
  • Anna F. Dominiczak
  • Mika Kivimaki
  • Michael G. Marmot
  • Tetsuro Miki
  • Danish Saleheen
  • Giriraj R. Chandak
  • Josef Coresh
  • Gerjan Navis
  • Veikko Salomaa
  • Bok Ghee Han
  • Xiaofeng Zhu
  • Jaspal S. Kooner
  • Olle Melander
  • Paul M. Ridker
  • Stefania Bandinelli
  • Ulf B. Gyllensten
  • Alan F. Wright
  • James F. Wilson
  • Luigi Ferrucci
  • Martin Farrall
  • Jaakko Tuomilehto
  • Peter P. Pramstaller
  • Roberto Elosua
  • Nicole Soranzo
  • Eric J.G. Sijbrands
  • David Altshuler
  • Ruth J F Loos
  • Alan R. Shuldiner
  • Christian Gieger
  • Pierre Meneton
  • Andre G. Uitterlinden
  • Nicholas J. Wareham
  • Vilmundur Gudnason
  • Jerome I. Rotter
  • Rainer Rettig
  • Manuela Uda
  • David P. Strachan
  • Jacqueline C.M. Witteman
  • Anna Liisa Hartikainen
  • Jacques S. Beckmann
  • Eric Boerwinkle
  • Ramachandran S. Vasan
  • Michael Boehnke
  • Martin G. Larson
  • Marjo-Riitta Järvelin
  • Bruce M. Psaty
  • Gonçalo R. Abecasis
  • Aravinda Chakravarti
  • Paul Elliott
  • Cornelia M. Van Duijn
  • Christopher Newton-Cheh
  • Daniel Levy
  • Mark J. Caulfield
  • Toby Johnson

Research units

  • Johns Hopkins University
  • University of Lausanne
  • University of Geneva
  • Queen Mary University of London
  • University of Washington
  • Harvard University
  • Icelandic Heart Association
  • University of Iceland
  • University of Leicester
  • Erasmus University Rotterdam
  • Netherland Genome Initiative (NGI)
  • Imperial College London
  • University of Michigan, Ann Arbor
  • University of Greifswald
  • Medical Research Council
  • CEA
  • University of Tartu
  • University of Maryland, Baltimore
  • King's College London
  • Pompeu Fabra University
  • European Academy Bozen/Bolzano (EURAC)
  • Affiliated Institute of the University of Lübeck
  • University of Oxford
  • University of Edinburgh
  • University of Split
  • Uppsala University
  • Amgen Incorporated
  • Lund University
  • University of Verona
  • London North West University Healthcare NHS Trust
  • University of Mississippi
  • University College London
  • Korea National Institute of Health
  • University of Groningen
  • CSIR - Biomedicine and Agriculture
  • University of Cambridge
  • Ehime University
  • St. George's University of London
  • Wake Forest University
  • Washington University St. Louis
  • University of Eastern Finland
  • Loyola University Chicago
  • University of California at San Francisco
  • Agency for Science, Technology and Research
  • National University of Singapore
  • Tampere University
  • University of Turin
  • Human Genetics Foundation (HuGeF)
  • Department of Genetics
  • University of North Carolina
  • University of Bristol
  • Utrecht University
  • University of Western Australia
  • Norwegian University of Science and Technology
  • MRC Unit for Lifelong Health and Ageing
  • University of Gothenburg
  • Glenfield Hospital
  • KU Leuven
  • Columbia University
  • Technische Universität Dresden
  • University of Ioannina
  • University of Texas Health Science Center at Houston
  • Washington Hospital Center
  • University of South Florida
  • University of Dundee
  • Path West Laboratory Medicine of Western Australia
  • Case Western Reserve University
  • University of Turku
  • University of San Carlos - Philippines
  • Boston University
  • University of Regensburg
  • University of Freiburg
  • Swiss Institute of Bioinformatics
  • Glaxo Smith Kline
  • University of Exeter
  • Aga Khan University
  • University of Lübeck
  • King Edward Memorial Hospital India
  • Broad Institute
  • National Institute for Health and Welfare
  • FIMM
  • Merck
  • Wellcome Sanger Institute
  • University of Utah
  • University of Southern California
  • University of Münster
  • Medical College of Georgia
  • Group Health Cooperative
  • VA Medical Center
  • Tallinn University of Technology
  • North Estonia Medical Centre
  • London School of Hygiene and Tropical Medicine
  • Public Health Foundation of India
  • University of Oslo
  • Tuscany Regional Health Agency
  • The University of the West Indies Kingston
  • University of Ibadan
  • National Cerebral and Cardiovascular Research Center
  • Shiga University of Medical Science
  • Osaka University
  • Tohoku University
  • Yokohama City University
  • Pontificia Universidad Catolica de Chile
  • Helmholtz Zentrum München - German Research Center for Environmental Health
  • Technical University of Munich
  • Ludwig Maximilian University of Munich
  • Cedars-Sinai Medical Center
  • Finnish Institute of Occupational Health
  • Lapland Central Hospital
  • Center for Non-Communicable Diseases
  • Karolinska Institutet
  • CNR
  • Divisione di Medicina
  • University of Oulu
  • Computational Medicine Research Group, Institute of Clinical Medicine
  • Institute of Molecular Medicine Finland FIMM
  • University of Helsinki
  • Universite Paris 13
  • Mayo Clinic Jacksonville, FL
  • Medical University of Silesia in Katowice
  • Federation University Australia
  • University of Zagreb
  • AstraZeneca Sweden
  • Ontario Institute for Cancer Research
  • University of Toronto
  • Singapore National Eye Center
  • University of Glasgow
  • Geriatric Rehabilitation Unit
  • South Ostrobothnia Central Hospital
  • Universidad Autónoma de Madrid
  • General Central Hospital
  • CIBER - Center for Biomedical Research Network
  • Institut National de la Santé et de la Recherche Médicale
  • Human Genetics Center
  • NGI Erasmus Medical Center
  • NHLBI, Bethesda, MD
  • National Institutes of Health

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.

Details

Original languageEnglish
Pages (from-to)103-109
Number of pages7
JournalNature
Volume478
Issue number7367
Publication statusPublished - 6 Oct 2011
MoE publication typeA1 Journal article-refereed

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