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Genome-wide association study identifies eight loci associated with blood pressure

Author

  • Christopher Newton-Cheh
  • Toby Johnson
  • Vesela Gateva
  • Martin D. Tobin
  • Murielle Bochud
  • Lachlan Coin
  • Samer S. Najjar
  • Jing Hua Zhao
  • Simon C. Heath
  • Susana Eyheramendy
  • Konstantinos Papadakis
  • Benjamin F. Voight
  • Laura J. Scott
  • Feng Zhang
  • Martin Farrall
  • Toshiko Tanaka
  • Chris Wallace
  • John C. Chambers
  • Kay-Tee Khaw
  • Peter Nilsson
  • Pim van der Harst
  • Silvia Polidoro
  • Diederick E. Grobbee
  • N. Charlotte Onland-Moret
  • Michiel L. Bots
  • Louise V. Wain
  • Katherine S. Elliott
  • Alexander Teumer
  • Jian'an Luan
  • Gavin Lucas
  • Johanna Kuusisto
  • Paul R. Burton
  • David Hadley
  • Wendy L. McArdle
  • Morris Brown
  • Anna Dominiczak
  • Stephen J. Newhouse
  • Nilesh J. Samani
  • John Webster
  • Eleftheria Zeggini
  • Jacques S. Beckmann
  • Sven Bergmann
  • Noha Lim
  • Kijoung Song
  • Peter Vollenweider
  • Gerard Waeber
  • Dawn M. Waterworth
  • Xin Yuan
  • Leif Groop
  • Marju Orho-Melander
  • Alessandra Allione
  • Alessandra Di Gregorio
  • Simonetta Guarrera
  • Salvatore Panico
  • Fulvio Ricceri
  • Valeria Romanazzi
  • Carlotta Sacerdote
  • Paolo Vineis
  • Ines Barroso
  • Manjinder S. Sandhu
  • Robert N. Luben
  • Gabriel J. Crawford
  • Pekka Jousilahti
  • Markus Perola
  • Michael Boehnke
  • Lori L. Bonnycastle
  • Francis S. Collins
  • Anne U. Jackson
  • Karen L. Mohlke
  • Heather M. Stringham
  • Timo T. Valle
  • Cristen J. Willer
  • Richard N. Bergman
  • Mario A. Morken
  • Angela Doering
  • Christian Gieger
  • Thomas Illig
  • Thomas Meitinger
  • Elin Org
  • Arne Pfeufer
  • H. Erich Wichmann
  • Sekar Kathiresan
  • Jaume Marrugat
  • Christopher J. O'Donnell
  • Stephen M. Schwartz
  • David S. Siscovick
  • Isaac Subirana
  • Nelson B. Freimer
  • Anna-Liisa Hartikainen
  • Mark I. McCarthy
  • Paul F. O'Reilly
  • Leena Peltonen
  • Anneli Pouta
  • Paul E. de Jong
  • Harold Snieder
  • Wiek H. van Gilst
  • Robert Clarke
  • Anuj Goel
  • Anders Hamsten
  • John F. Peden
  • Udo Seedorf
  • Ann-Christine Syvanen
  • Giovanni Tognoni
  • Edward G. Lakatta
  • Serena Sanna
  • Paul Scheet
  • David Schlessinger
  • Angelo Scuteri
  • Marcus Doerr
  • Florian Ernst
  • Stephan B. Felix
  • Georg Homuth
  • Roberto Lorbeer
  • Thorsten Reffelmann
  • Rainer Rettig
  • Uwe Voelker
  • Pilar Galan
  • Ivo G. Gut
  • Serge Hercberg
  • G. Mark Lathrop
  • Diana Zelenika
  • Panos Deloukas
  • Nicole Soranzo
  • Frances M. Williams
  • Guangju Zhai
  • Veikko Salomaa
  • Markku Laakso
  • Roberto Elosua
  • Nita G. Forouhi
  • Henry Volzke
  • Cuno S. Uiterwaal
  • Yvonne T. van der Schouw
  • Mattijs E. Numans
  • Giuseppe Matullo
  • Gerjan Navis
  • Göran Berglund
  • Sheila A. Bingham
  • Jaspal S. Kooner
  • John M. Connell
  • Stefania Bandinelli
  • Luigi Ferrucci
  • Hugh Watkins
  • Tim D. Spector
  • Jaakko Tuomilehto
  • David Altshuler
  • David P. Strachan
  • Maris Laan
  • Pierre Meneton
  • Nicholas J. Wareham
  • Manuela Uda
  • Marjo-Riitta Jarvelin
  • Vincent Mooser
  • Olle Melander
  • Ruth J. F. Loos
  • Paul Elliott
  • Goncalo R. Abecasis
  • Mark Caulfield
  • Patricia B. Munroe

Summary, in English

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

Publishing year

2009

Language

English

Pages

666-676

Publication/Series

Nature Genetics

Volume

41

Issue

6

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Other Clinical Medicine
  • Endocrinology and Diabetes
  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Internal Medicine - Epidemiology
  • Translational Muscle Research
  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 1546-1718