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

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

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Authors

  • Georg B. Ehret
  • Patricia B. Munroe
  • Kenneth M. Rice
  • Murielle Bochud
  • Andrew D. Johnson
  • Daniel I. Chasman
  • Albert V. 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 Aulchenko
  • 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 Sjogren
  • D. G. Vinay
  • Myriam Alexander
  • Yasuharu Tabara
  • Sue Shaw-Hawkins
  • Peter H. Whincup
  • Yongmei Liu
  • Gang Shi
  • Johanna Kuusisto
  • Bamidele Tayo
  • Mark Seielstad
  • Xueling Sim
  • [No Value] Khanh-Dung Hoang Nguyen
  • Terho Lehtimaki
  • 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 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
  • 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 Kahonen
  • 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
  • Juergen Graessler
  • Leif Groop
  • Benjamin F. Voight
  • Johannes Kettunen
  • Philip Howard
  • Andrew Taylor
  • Simonetta Guarrera
  • Fulvio Ricceri
  • Valur Emilsson
  • Andrew Plump
  • Ine S. 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 Scott
  • Joban S. Sehmi
  • Weihua Zhang
  • Bo Hedblad
  • Peter Nilsson
  • George Davey Smith
  • Andrew Wong
  • Narisu Narisu
  • Alena Stancakova
  • 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 Lyytikainen
  • Pasi Soininen
  • Taru Tukiainen
  • Peter Wurtz
  • Rick Twee-Hee Ong
  • Marcus Doerr
  • Heyo K. Kroemer
  • Uwe Voelker
  • Henry Voelzke
  • 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 Jarvelin
  • Bruce M. Psaty
  • Goncalo R. Abecasis
  • Aravinda Chakravarti
  • Paul Elliott
  • Cornelia M. van Duijn
  • Christopher Newton-Cheh
  • Daniel Levy
  • Mark J. Caulfield
  • Toby Johnson
  • CARDIoGRAM Consortium, KidneyGen Consortium, EchoGen Consortium, CKDGen Consortium, Int Consortium Blood Pressure Geno, CHARGE-HF Consortium

Research units

Info

Original languageEnglish
Pages103-109
Number of pages7
JournalNature
Journal publication date6 Oct 2011
Volume478
Issue7367
DOIs
StatePublished

Abstract

Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). 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.

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