Novel blood pressure locus and gene discovery using genome-wide association study and expression data sets from blood and the kidney

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Authors

  • Louise V. Wain
  • Ahmad Vaez
  • Rick Jansen
  • Roby Joehanes
  • Peter J. Van Der Most
  • A. Mesut Erzurumluoglu
  • And 237 others
  • Paul F. O'Reilly
  • Claudia P. Cabrera
  • Helen R. Warren
  • Lynda M. Rose
  • Germaine C. Verwoert
  • Jouke Jan Hottenga
  • Rona J. Strawbridge
  • Tonu Esko
  • Dan E. Arking
  • Shih Jen Hwang
  • Xiuqing Guo
  • Zoltan Kutalik
  • Stella Trompet
  • Nick Shrine
  • Alexander Teumer
  • Janina S. Ried
  • Joshua C. Bis
  • Albert Vernon Smith
  • Najaf Amin
  • Ilja M. Nolte
  • Leo Pekka Lyytikäinen
  • Anubha Mahajan
  • Nicholas J. Wareham
  • Edith Hofer
  • Peter K. Joshi
  • Kati Kristiansson
  • Michela Traglia
  • Aki S. Havulinna
  • Anuj Goel
  • Mike A. Nalls
  • Siim Sõber
  • Dragana Vuckovic
  • Jian'An Luan
  • Fabiola M. Del Greco
  • Kristin L. Ayers
  • Jaume Marrugat
  • Daniela Ruggiero
  • Lorna M. Lopez
  • Teemu Niiranen
  • Stefan Enroth
  • Anne U. Jackson
  • Christopher P. Nelson
  • Jennifer E. Huffman
  • Weihua Zhang
  • Jonathan Marten
  • Ilaria Gandin
  • Sarah E. Harris
  • Tatijana Zemunik
  • Yingchang Lu
  • Evangelos Evangelou
  • Nabi Shah
  • Martin H. De Borst
  • Massimo Mangino
  • Bram P. Prins
  • Archie Campbell
  • Ruifang Li-Gao
  • Ganesh Chauhan
  • Christopher Oldmeadow
  • Gonçalo Abecasis
  • Maryam Abedi
  • Caterina M. Barbieri
  • Michael R. Barnes
  • Chiara Batini
  • John Beilby
  • Tineka Blake
  • Michael Boehnke
  • Erwin P. Bottinger
  • Peter S. Braund
  • Morris J. Brown
  • Marco Brumat
  • Harry Campbell
  • John C. Chambers
  • Massimiliano Cocca
  • Francis S. Collins
  • John Connell
  • Heather J. Cordell
  • Jeffrey J. Damman
  • Gail Davies
  • Eco J C N De Geus
  • Renée De Mutsert
  • Joris Deelen
  • Yusuf Demirkale
  • Alex S.F. Doney
  • Marcus Dörr
  • Martin Farrall
  • Teresa Ferreira
  • Mattias Frånberg
  • He Gao
  • Vilmantas Giedraitis
  • Christian Gieger
  • Franco Giulianini
  • Alan J. Gow
  • Anders Hamsten
  • Tamara B. Harris
  • Albert Hofman
  • Elizabeth G. Holliday
  • Jennie Hui
  • Marjo Riitta Jarvelin
  • Åsa Johansson
  • Andrew D. Johnson
  • Pekka Jousilahti
  • Antti Jula
  • Mika Kähönen
  • Sekar Kathiresan
  • Kay Tee Khaw
  • Ivana Kolcic
  • Seppo Koskinen
  • Claudia Langenberg
  • Marty Larson
  • Lenore J. Launer
  • Benjamin Lehne
  • David C M Liewald
  • Li Lin
  • Lars Lind
  • François Mach
  • Chrysovalanto Mamasoula
  • Cristina Menni
  • Borbala Mifsud
  • Yuri Milaneschi
  • Anna Morgan
  • Andrew D. Morris
  • Alanna C. Morrison
  • Peter J. Munson
  • Priyanka Nandakumar
  • Quang Tri Nguyen
  • Teresa Nutile
  • Albertine J. Oldehinkel
  • Ben A. Oostra
  • Elin Org
  • Sandosh Padmanabhan
  • Aarno Palotie
  • Guillaume Paré
  • Alison Pattie
  • Brenda W J H Penninx
  • Neil Poulter
  • Peter P. Pramstaller
  • Olli T. Raitakari
  • Meixia Ren
  • Kenneth M. Rice
  • Paul M. Ridker
  • Harriëtte Riese
  • Samuli Ripatti
  • Antonietta Robino
  • Jerome I. Rotter
  • Igor Rudan
  • Yasaman Saba
  • Aude Saint-Pierre
  • Cinzia F. Sala
  • Antti Pekka Sarin
  • Reinhold Schmidt
  • Rodney Scott
  • Marc A. Seelen
  • Denis C. Shields
  • David S. Siscovick
  • Rossella Sorice
  • Alice Stanton
  • David J. Stott
  • Johan Sundström
  • Morris A. Swertz
  • Kent D. Taylor
  • Simon Thom
  • Ioanna Tzoulaki
  • Christophe Tzourio
  • André G. Uitterlinden
  • Uwe Völker
  • Peter Vollenweider
  • Sarah H. Wild
  • Gonneke Willemsen
  • Alan F. Wright
  • Jie Yao
  • Sébastien Thériault
  • David Conen
  • John Attia
  • Peter Sever
  • Stéphanie Debette
  • Dennis O. Mook-Kanamori
  • Eleftheria Zeggini
  • Tim D Spector
  • Pim Van der Harst
  • Colin N A Palmer
  • Anne Claire Vergnaud
  • Ruth J F Loos
  • Ozren Polasek
  • John M. Starr
  • Giorgia Girotto
  • Caroline Hayward
  • Jaspal S. Kooner
  • Cecila M. Lindgren
  • Veronique Vitart
  • Nilesh J. Samani
  • Jaakko Tuomilehto
  • Ulf Gyllensten
  • Paul B. Knekt
  • Ian J. Deary
  • Marina Ciullo
  • Roberto Elosua
  • Bernard D. Keavney
  • Andrew A. Hicks
  • Robert A. Scott
  • Paolo Gasparini
  • Maris Laan
  • Yongmei Liu
  • Hugh Watkins
  • Catharina A. Hartman
  • Veikko Salomaa
  • Daniela Toniolo
  • Markus Perola
  • James F. Wilson
  • Helena Schmidt
  • Jing Hua Zhao
  • Terho Lehtimäki
  • Cornelia M. van Duijn
  • Vilmundur Gudnason
  • Bruce M. Psaty
  • Annette Peters
  • Rainer Rettig
  • Alan James
  • J. Wouter Jukema
  • David P. Strachan
  • Walter Palmas
  • Andres Metspalu
  • Erik Ingelsson
  • Dorret I. Boomsma
  • Oscar H. Franco
  • Murielle Bochud
  • Christopher Newton-Cheh
  • Patricia B. Munroe
  • Paul Elliott
  • Daniel I. Chasman
  • Aravinda Chakravarti
  • Joanne Knight
  • Andrew P. Morris
  • Daniel Levy
  • Martin D. Tobin
  • Harold Snieder
  • Mark J. Caulfield
  • Georg B. Ehret

Research units

Abstract

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.

Peer-reviewedYes
Original languageEnglish
Pages (from-to)e4-e19
JournalHypertension
Volume70
Issue number3
DOIs
StatePublished - 1 Sep 2017


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