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The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66... Full description

Journal Title: Nature Genetics 2016
Main Author: Georg B Ehret
Other Authors: Teresa Ferreira , Daniel I Chasman , Anne U Jackson , Ellen M Schmidt , Toby Johnson , Gudmar Thorleifsson , Jian'An Luan , Louise A Donnelly , Stavroula Kanoni , Ann-Kristin Petersen , Vasyl Pihur , Rona J Strawbridge , Dmitry Shungin , Maria F Hughes , Osorio Meirelles , Marika Kaakinen , Nabila Bouatia-Naji , Kati Kristiansson , Sonia Shah , Marcus E Kleber , Xiuqing Guo , Leo-Pekka Lyytikäinen , Cristiano Fava , Niclas Eriksson , Ilja M Nolte , Patrik K Magnusson , Elias L Salfati , Loukianos S Rallidis , Elizabeth Theusch , Andrew J P Smith , Lasse Folkersen , Kate Witkowska , Tune H Pers , Roby Joehanes , Stuart K Kim , Lazaros Lataniotis , Rick Jansen , Andrew D Johnson , Helen Warren , Young Jin Kim , Wei Zhao , Ying Wu , Bamidele O Tayo , Murielle Bochud , Devin Absher , Linda S Adair , Najaf Amin , Dan E Arking , Tomas Axelsson , Damiano Baldassarre , Beverley Balkau , Stefania Bandinelli , Michael R Barnes , Inês Barroso , Stephen Bevan , Joshua C Bis , Gyda Bjornsdottir , Michael Boehnke , Eric Boerwinkle , Lori L Bonnycastle , Dorret I Boomsma , Stefan R Bornstein , Morris J Brown , Michel Burnier , Claudia P Cabrera , John C Chambers , I-Shou Chang , Ching-Yu Cheng , Peter S Chines , Ren-Hua Chung , Francis S Collins , John M Connell , Angela Döring , Jean Dallongeville , John Danesh , Ulf De Faire , Graciela Delgado , Anna F Dominiczak , Alex S F Doney , Fotios Drenos , Sarah Edkins , John D Eicher , Roberto Elosua , Stefan Enroth , Jeanette Erdmann , Per Eriksson , Tonu Esko , Evangelos Evangelou , Alun Evans , Tove Fall , Martin Farrall , Janine F Felix , Jean Ferrières , Luigi Ferrucci , Myriam Fornage , Terrence Forrester , Nora Franceschini , Oscar H Franco , Anders Franco-Cereceda , Ross M Fraser , Santhi K Ganesh , He Gao , Karl Gertow , Francesco Gianfagna , Bruna Gigante , Franco Giulianini , Anuj Goel , Alison H Goodall , Mark O Goodarzi , Mathias Gorski , Jürgen Gräßler , Christopher J Groves , Vilmundur Gudnason , Ulf Gyllensten , Göran Hallmans , Anna-Liisa Hartikainen , Maija Hassinen , Aki S Havulinna , Caroline Hayward , Serge Hercberg , Karl-Heinz Herzig , Andrew A Hicks , Aroon D Hingorani , Joel N Hirschhorn , Albert Hofman , Jostein Holmen , Oddgeir Lingaas Holmen , Jouke-Jan Hottenga , Phil Howard , Chao A Hsiung , Steven C Hunt , M Arfan Ikram , Thomas Illig , Carlos Iribarren , Richard A Jensen , Mika Kähönen , Hyun Min Kang , Sekar Kathiresan , Brendan J Keating , Kay-Tee Khaw , Yun Kyoung Kim , Eric Kim , Mika Kivimaki , Norman Klopp , Genovefa Kolovou , Pirjo Komulainen , Jaspal S Kooner , Gulum Kosova , Ronald M Krauss , Diana Kuh , Zoltan Kutalik , Johanna Kuusisto , Kirsti Kvaløy , Timo A Lakka , Nanette R Lee , I-Te Lee , Wen-Jane Lee , Daniel Levy , Xiaohui Li , Kae-Woei Liang , Honghuang Lin , Li Lin , Jaana Lindström , Stéphane Lobbens , Satu Männistö , Gabriele Müller , Martina Müller-Nurasyid , François Mach , Hugh S Markus , Eirini Marouli , Mark I Mccarthy , Colin A Mckenzie , Pierre Meneton , Cristina Menni , Andres Metspalu , Vladan Mijatovic , Leena Moilanen , May E Montasser , Andrew D Morris , Alanna C Morrison , Antonella Mulas , Ramaiah Nagaraja , Narisu Narisu , Kjell Nikus , Christopher J O'Donnell , Paul F O'Reilly , Ken K Ong , Fred Paccaud , Cameron D Palmer , Afshin Parsa , Nancy L Pedersen , Brenda W Penninx , Markus Perola , Annette Peters , Neil Poulter , Peter P Pramstaller , Bruce M Psaty , Thomas Quertermous , Dabeeru C Rao , Asif Rasheed , N William Rayner , Frida Renström , Rainer Rettig , Kenneth M Rice , Robert Roberts , Lynda M Rose , Jacques Rossouw , Nilesh J Samani , Serena Sanna , Jouko Saramies , Heribert Schunkert , Sylvain Sebert , Wayne H-H Sheu , Young-Ah Shin , Xueling Sim , Johannes H Smit , Albert V Smith , Maria X Sosa , Tim D Spector , Alena Stančáková , Alice V Stanton , Kathleen E Stirrups , Heather M Stringham , Johan Sundstrom , Amy J Swift , Ann-Christine Syvänen , E-Shyong Tai , Toshiko Tanaka , Kirill V Tarasov , Alexander Teumer , Unnur Thorsteinsdottir , Martin D Tobin , Elena Tremoli , Andre G Uitterlinden , Matti Uusitupa , Ahmad Vaez , Dhananjay Vaidya , Cornelia M Van Duijn , Erik P A Van Iperen , Ramachandran S Vasan , Germaine C Verwoert , Jarmo Virtamo , Veronique Vitart , Benjamin F Voight , Peter Vollenweider , Aline Wagner , Louise V Wain , Nicholas J Wareham , Hugh Watkins , Alan B Weder , Harm-Jan Westra , Rainford Wilks , Tom Wilsgaard , James F Wilson , Tien Y Wong , Tsun-Po Yang , Jie Yao , Loic Yengo , Weihua Zhang , Jing Hua Zhao , Xiaofeng Zhu , Pascal Bovet , Richard S Cooper , Karen L Mohlke , Danish Saleheen , Jong-Young Lee , Paul Elliott , Hinco J Gierman , Cristen J Willer , Lude Franke , G Kees Hovingh , Kent D Taylor , George Dedoussis , Peter Sever , Andrew Wong , Lars Lind , Themistocles L Assimes , Inger Njølstad , Peter E H Schwarz , Claudia Langenberg , Harold Snieder , Mark J Caulfield , Olle Melander , Markku Laakso , Juha Saltevo , Rainer Rauramaa , Jaakko Tuomilehto , Erik Ingelsson , Terho Lehtimäki , Kristian Hveem , Walter Palmas , Winfried März , Meena Kumari , Veikko Salomaa , Yii-Der I Chen , Jerome I Rotter , Philippe Froguel , Marjo-Riitta Jarvelin , Edward G Lakatta , Kari Kuulasmaa , Paul W Franks , Anders Hamsten , H-Erich Wichmann , Colin N A Palmer , Kari Stefansson , Paul M Ridker , Ruth J F Loos , Aravinda Chakravarti , Panos Deloukas , Andrew P Morris , Christopher Newton-Cheh , Patricia B Munroe
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ID: ISSN: 1061-4036 ; E-ISSN: 1546-1718 ; DOI: 10.1038/ng.3667
Link: http://dx.doi.org/10.1038/ng.3667
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recordid: nature_a10.1038/ng.3667
title: The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
format: Article
creator:
  • Georg B Ehret
  • Teresa Ferreira
  • Daniel I Chasman
  • Anne U Jackson
  • Ellen M Schmidt
  • Toby Johnson
  • Gudmar Thorleifsson
  • Jian'An Luan
  • Louise A Donnelly
  • Stavroula Kanoni
  • Ann-Kristin Petersen
  • Vasyl Pihur
  • Rona J Strawbridge
  • Dmitry Shungin
  • Maria F Hughes
  • Osorio Meirelles
  • Marika Kaakinen
  • Nabila Bouatia-Naji
  • Kati Kristiansson
  • Sonia Shah
  • Marcus E Kleber
  • Xiuqing Guo
  • Leo-Pekka Lyytikäinen
  • Cristiano Fava
  • Niclas Eriksson
  • Ilja M Nolte
  • Patrik K Magnusson
  • Elias L Salfati
  • Loukianos S Rallidis
  • Elizabeth Theusch
  • Andrew J P Smith
  • Lasse Folkersen
  • Kate Witkowska
  • Tune H Pers
  • Roby Joehanes
  • Stuart K Kim
  • Lazaros Lataniotis
  • Rick Jansen
  • Andrew D Johnson
  • Helen Warren
  • Young Jin Kim
  • Wei Zhao
  • Ying Wu
  • Bamidele O Tayo
  • Murielle Bochud
  • Devin Absher
  • Linda S Adair
  • Najaf Amin
  • Dan E Arking
  • Tomas Axelsson
  • Damiano Baldassarre
  • Beverley Balkau
  • Stefania Bandinelli
  • Michael R Barnes
  • Inês Barroso
  • Stephen Bevan
  • Joshua C Bis
  • Gyda Bjornsdottir
  • Michael Boehnke
  • Eric Boerwinkle
  • Lori L Bonnycastle
  • Dorret I Boomsma
  • Stefan R Bornstein
  • Morris J Brown
  • Michel Burnier
  • Claudia P Cabrera
  • John C Chambers
  • I-Shou Chang
  • Ching-Yu Cheng
  • Peter S Chines
  • Ren-Hua Chung
  • Francis S Collins
  • John M Connell
  • Angela Döring
  • Jean Dallongeville
  • John Danesh
  • Ulf De Faire
  • Graciela Delgado
  • Anna F Dominiczak
  • Alex S F Doney
  • Fotios Drenos
  • Sarah Edkins
  • John D Eicher
  • Roberto Elosua
  • Stefan Enroth
  • Jeanette Erdmann
  • Per Eriksson
  • Tonu Esko
  • Evangelos Evangelou
  • Alun Evans
  • Tove Fall
  • Martin Farrall
  • Janine F Felix
  • Jean Ferrières
  • Luigi Ferrucci
  • Myriam Fornage
  • Terrence Forrester
  • Nora Franceschini
  • Oscar H Franco
  • Anders Franco-Cereceda
  • Ross M Fraser
  • Santhi K Ganesh
  • He Gao
  • Karl Gertow
  • Francesco Gianfagna
  • Bruna Gigante
  • Franco Giulianini
  • Anuj Goel
  • Alison H Goodall
  • Mark O Goodarzi
  • Mathias Gorski
  • Jürgen Gräßler
  • Christopher J Groves
  • Vilmundur Gudnason
  • Ulf Gyllensten
  • Göran Hallmans
  • Anna-Liisa Hartikainen
  • Maija Hassinen
  • Aki S Havulinna
  • Caroline Hayward
  • Serge Hercberg
  • Karl-Heinz Herzig
  • Andrew A Hicks
  • Aroon D Hingorani
  • Joel N Hirschhorn
  • Albert Hofman
  • Jostein Holmen
  • Oddgeir Lingaas Holmen
  • Jouke-Jan Hottenga
  • Phil Howard
  • Chao A Hsiung
  • Steven C Hunt
  • M Arfan Ikram
  • Thomas Illig
  • Carlos Iribarren
  • Richard A Jensen
  • Mika Kähönen
  • Hyun Min Kang
  • Sekar Kathiresan
  • Brendan J Keating
  • Kay-Tee Khaw
  • Yun Kyoung Kim
  • Eric Kim
  • Mika Kivimaki
  • Norman Klopp
  • Genovefa Kolovou
  • Pirjo Komulainen
  • Jaspal S Kooner
  • Gulum Kosova
  • Ronald M Krauss
  • Diana Kuh
  • Zoltan Kutalik
  • Johanna Kuusisto
  • Kirsti Kvaløy
  • Timo A Lakka
  • Nanette R Lee
  • I-Te Lee
  • Wen-Jane Lee
  • Daniel Levy
  • Xiaohui Li
  • Kae-Woei Liang
  • Honghuang Lin
  • Li Lin
  • Jaana Lindström
  • Stéphane Lobbens
  • Satu Männistö
  • Gabriele Müller
  • Martina Müller-Nurasyid
  • François Mach
  • Hugh S Markus
  • Eirini Marouli
  • Mark I Mccarthy
  • Colin A Mckenzie
  • Pierre Meneton
  • Cristina Menni
  • Andres Metspalu
  • Vladan Mijatovic
  • Leena Moilanen
  • May E Montasser
  • Andrew D Morris
  • Alanna C Morrison
  • Antonella Mulas
  • Ramaiah Nagaraja
  • Narisu Narisu
  • Kjell Nikus
  • Christopher J O'Donnell
  • Paul F O'Reilly
  • Ken K Ong
  • Fred Paccaud
  • Cameron D Palmer
  • Afshin Parsa
  • Nancy L Pedersen
  • Brenda W Penninx
  • Markus Perola
  • Annette Peters
  • Neil Poulter
  • Peter P Pramstaller
  • Bruce M Psaty
  • Thomas Quertermous
  • Dabeeru C Rao
  • Asif Rasheed
  • N William Rayner
  • Frida Renström
  • Rainer Rettig
  • Kenneth M Rice
  • Robert Roberts
  • Lynda M Rose
  • Jacques Rossouw
  • Nilesh J Samani
  • Serena Sanna
  • Jouko Saramies
  • Heribert Schunkert
  • Sylvain Sebert
  • Wayne H-H Sheu
  • Young-Ah Shin
  • Xueling Sim
  • Johannes H Smit
  • Albert V Smith
  • Maria X Sosa
  • Tim D Spector
  • Alena Stančáková
  • Alice V Stanton
  • Kathleen E Stirrups
  • Heather M Stringham
  • Johan Sundstrom
  • Amy J Swift
  • Ann-Christine Syvänen
  • E-Shyong Tai
  • Toshiko Tanaka
  • Kirill V Tarasov
  • Alexander Teumer
  • Unnur Thorsteinsdottir
  • Martin D Tobin
  • Elena Tremoli
  • Andre G Uitterlinden
  • Matti Uusitupa
  • Ahmad Vaez
  • Dhananjay Vaidya
  • Cornelia M Van Duijn
  • Erik P A Van Iperen
  • Ramachandran S Vasan
  • Germaine C Verwoert
  • Jarmo Virtamo
  • Veronique Vitart
  • Benjamin F Voight
  • Peter Vollenweider
  • Aline Wagner
  • Louise V Wain
  • Nicholas J Wareham
  • Hugh Watkins
  • Alan B Weder
  • Harm-Jan Westra
  • Rainford Wilks
  • Tom Wilsgaard
  • James F Wilson
  • Tien Y Wong
  • Tsun-Po Yang
  • Jie Yao
  • Loic Yengo
  • Weihua Zhang
  • Jing Hua Zhao
  • Xiaofeng Zhu
  • Pascal Bovet
  • Richard S Cooper
  • Karen L Mohlke
  • Danish Saleheen
  • Jong-Young Lee
  • Paul Elliott
  • Hinco J Gierman
  • Cristen J Willer
  • Lude Franke
  • G Kees Hovingh
  • Kent D Taylor
  • George Dedoussis
  • Peter Sever
  • Andrew Wong
  • Lars Lind
  • Themistocles L Assimes
  • Inger Njølstad
  • Peter E H Schwarz
  • Claudia Langenberg
  • Harold Snieder
  • Mark J Caulfield
  • Olle Melander
  • Markku Laakso
  • Juha Saltevo
  • Rainer Rauramaa
  • Jaakko Tuomilehto
  • Erik Ingelsson
  • Terho Lehtimäki
  • Kristian Hveem
  • Walter Palmas
  • Winfried März
  • Meena Kumari
  • Veikko Salomaa
  • Yii-Der I Chen
  • Jerome I Rotter
  • Philippe Froguel
  • Marjo-Riitta Jarvelin
  • Edward G Lakatta
  • Kari Kuulasmaa
  • Paul W Franks
  • Anders Hamsten
  • H-Erich Wichmann
  • Colin N A Palmer
  • Kari Stefansson
  • Paul M Ridker
  • Ruth J F Loos
  • Aravinda Chakravarti
  • Panos Deloukas
  • Andrew P Morris
  • Christopher Newton-Cheh
  • Patricia B Munroe
subjects:
  • Science & Technology
  • Life Sciences & Biomedicine
  • Genetics & Heredity
  • Genome-Wide Association
  • Arterial-Hypertension
  • Common Variants
  • Cell-Types
  • Loci
  • Traits
  • Chromatin
  • Susceptibility
  • Metaanalysis
  • Biology
  • African Continental Ancestry Group
  • Asian Continental Ancestry Group
  • Blood Pressure
  • Cells, Cultured
  • Genome-Wide Association Study
  • Humans
  • Hypertension
  • Microarray Analysis
  • Polymorphism, Single Nucleotide
  • Charge-Echogen Consortium
  • Charge-Hf Consortium
  • Wellcome Trust Case Control Consortium
  • Developmental Biology
  • 11 Medical And Health Sciences
  • 06 Biological Sciences
ispartof: Nature Genetics, 2016
description: To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.
language:
source:
identifier: ISSN: 1061-4036 ; E-ISSN: 1546-1718 ; DOI: 10.1038/ng.3667
fulltext: fulltext
issn:
  • 1061-4036
  • 10614036
  • 1546-1718
  • 15461718
url: Link


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titleThe genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
creatorGeorg B Ehret ; Teresa Ferreira ; Daniel I Chasman ; Anne U Jackson ; Ellen M Schmidt ; Toby Johnson ; Gudmar Thorleifsson ; Jian'An Luan ; Louise A Donnelly ; Stavroula Kanoni ; Ann-Kristin Petersen ; Vasyl Pihur ; Rona J Strawbridge ; Dmitry Shungin ; Maria F Hughes ; Osorio Meirelles ; Marika Kaakinen ; Nabila Bouatia-Naji ; Kati Kristiansson ; Sonia Shah ; Marcus E Kleber ; Xiuqing Guo ; Leo-Pekka Lyytikäinen ; Cristiano Fava ; Niclas Eriksson ; Ilja M Nolte ; Patrik K Magnusson ; Elias L Salfati ; Loukianos S Rallidis ; Elizabeth Theusch ; Andrew J P Smith ; Lasse Folkersen ; Kate Witkowska ; Tune H Pers ; Roby Joehanes ; Stuart K Kim ; Lazaros Lataniotis ; Rick Jansen ; Andrew D Johnson ; Helen Warren ; Young Jin Kim ; Wei Zhao ; Ying Wu ; Bamidele O Tayo ; Murielle Bochud ; Devin Absher ; Linda S Adair ; Najaf Amin ; Dan E Arking ; Tomas Axelsson ; Damiano Baldassarre ; Beverley Balkau ; Stefania Bandinelli ; Michael R Barnes ; Inês Barroso ; Stephen Bevan ; Joshua C Bis ; Gyda Bjornsdottir ; Michael Boehnke ; Eric Boerwinkle ; Lori L Bonnycastle ; Dorret I Boomsma ; Stefan R Bornstein ; Morris J Brown ; Michel Burnier ; Claudia P Cabrera ; John C Chambers ; I-Shou Chang ; Ching-Yu Cheng ; Peter S Chines ; Ren-Hua Chung ; Francis S Collins ; John M Connell ; Angela Döring ; Jean Dallongeville ; John Danesh ; Ulf De Faire ; Graciela Delgado ; Anna F Dominiczak ; Alex S F Doney ; Fotios Drenos ; Sarah Edkins ; John D Eicher ; Roberto Elosua ; Stefan Enroth ; Jeanette Erdmann ; Per Eriksson ; Tonu Esko ; Evangelos Evangelou ; Alun Evans ; Tove Fall ; Martin Farrall ; Janine F Felix ; Jean Ferrières ; Luigi Ferrucci ; Myriam Fornage ; Terrence Forrester ; Nora Franceschini ; Oscar H Franco ; Anders Franco-Cereceda ; Ross M Fraser ; Santhi K Ganesh ; He Gao ; Karl Gertow ; Francesco Gianfagna ; Bruna Gigante ; Franco Giulianini ; Anuj Goel ; Alison H Goodall ; Mark O Goodarzi ; Mathias Gorski ; Jürgen Gräßler ; Christopher J Groves ; Vilmundur Gudnason ; Ulf Gyllensten ; Göran Hallmans ; Anna-Liisa Hartikainen ; Maija Hassinen ; Aki S Havulinna ; Caroline Hayward ; Serge Hercberg ; Karl-Heinz Herzig ; Andrew A Hicks ; Aroon D Hingorani ; Joel N Hirschhorn ; Albert Hofman ; Jostein Holmen ; Oddgeir Lingaas Holmen ; Jouke-Jan Hottenga ; Phil Howard ; Chao A Hsiung ; Steven C Hunt ; M Arfan Ikram ; Thomas Illig ; Carlos Iribarren ; Richard A Jensen ; Mika Kähönen ; Hyun Min Kang ; Sekar Kathiresan ; Brendan J Keating ; Kay-Tee Khaw ; Yun Kyoung Kim ; Eric Kim ; Mika Kivimaki ; Norman Klopp ; Genovefa Kolovou ; Pirjo Komulainen ; Jaspal S Kooner ; Gulum Kosova ; Ronald M Krauss ; Diana Kuh ; Zoltan Kutalik ; Johanna Kuusisto ; Kirsti Kvaløy ; Timo A Lakka ; Nanette R Lee ; I-Te Lee ; Wen-Jane Lee ; Daniel Levy ; Xiaohui Li ; Kae-Woei Liang ; Honghuang Lin ; Li Lin ; Jaana Lindström ; Stéphane Lobbens ; Satu Männistö ; Gabriele Müller ; Martina Müller-Nurasyid ; François Mach ; Hugh S Markus ; Eirini Marouli ; Mark I Mccarthy ; Colin A Mckenzie ; Pierre Meneton ; Cristina Menni ; Andres Metspalu ; Vladan Mijatovic ; Leena Moilanen ; May E Montasser ; Andrew D Morris ; Alanna C Morrison ; Antonella Mulas ; Ramaiah Nagaraja ; Narisu Narisu ; Kjell Nikus ; Christopher J O'Donnell ; Paul F O'Reilly ; Ken K Ong ; Fred Paccaud ; Cameron D Palmer ; Afshin Parsa ; Nancy L Pedersen ; Brenda W Penninx ; Markus Perola ; Annette Peters ; Neil Poulter ; Peter P Pramstaller ; Bruce M Psaty ; Thomas Quertermous ; Dabeeru C Rao ; Asif Rasheed ; N William Rayner ; Frida Renström ; Rainer Rettig ; Kenneth M Rice ; Robert Roberts ; Lynda M Rose ; Jacques Rossouw ; Nilesh J Samani ; Serena Sanna ; Jouko Saramies ; Heribert Schunkert ; Sylvain Sebert ; Wayne H-H Sheu ; Young-Ah Shin ; Xueling Sim ; Johannes H Smit ; Albert V Smith ; Maria X Sosa ; Tim D Spector ; Alena Stančáková ; Alice V Stanton ; Kathleen E Stirrups ; Heather M Stringham ; Johan Sundstrom ; Amy J Swift ; Ann-Christine Syvänen ; E-Shyong Tai ; Toshiko Tanaka ; Kirill V Tarasov ; Alexander Teumer ; Unnur Thorsteinsdottir ; Martin D Tobin ; Elena Tremoli ; Andre G Uitterlinden ; Matti Uusitupa ; Ahmad Vaez ; Dhananjay Vaidya ; Cornelia M Van Duijn ; Erik P A Van Iperen ; Ramachandran S Vasan ; Germaine C Verwoert ; Jarmo Virtamo ; Veronique Vitart ; Benjamin F Voight ; Peter Vollenweider ; Aline Wagner ; Louise V Wain ; Nicholas J Wareham ; Hugh Watkins ; Alan B Weder ; Harm-Jan Westra ; Rainford Wilks ; Tom Wilsgaard ; James F Wilson ; Tien Y Wong ; Tsun-Po Yang ; Jie Yao ; Loic Yengo ; Weihua Zhang ; Jing Hua Zhao ; Xiaofeng Zhu ; Pascal Bovet ; Richard S Cooper ; Karen L Mohlke ; Danish Saleheen ; Jong-Young Lee ; Paul Elliott ; Hinco J Gierman ; Cristen J Willer ; Lude Franke ; G Kees Hovingh ; Kent D Taylor ; George Dedoussis ; Peter Sever ; Andrew Wong ; Lars Lind ; Themistocles L Assimes ; Inger Njølstad ; Peter E H Schwarz ; Claudia Langenberg ; Harold Snieder ; Mark J Caulfield ; Olle Melander ; Markku Laakso ; Juha Saltevo ; Rainer Rauramaa ; Jaakko Tuomilehto ; Erik Ingelsson ; Terho Lehtimäki ; Kristian Hveem ; Walter Palmas ; Winfried März ; Meena Kumari ; Veikko Salomaa ; Yii-Der I Chen ; Jerome I Rotter ; Philippe Froguel ; Marjo-Riitta Jarvelin ; Edward G Lakatta ; Kari Kuulasmaa ; Paul W Franks ; Anders Hamsten ; H-Erich Wichmann ; Colin N A Palmer ; Kari Stefansson ; Paul M Ridker ; Ruth J F Loos ; Aravinda Chakravarti ; Panos Deloukas ; Andrew P Morris ; Christopher Newton-Cheh ; Patricia B Munroe
ispartofNature Genetics, 2016
identifier
source
descriptionTo dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.
subjectScience & Technology ; Life Sciences & Biomedicine ; Genetics & Heredity ; Genome-Wide Association ; Arterial-Hypertension ; Common Variants ; Cell-Types ; Loci ; Traits ; Chromatin ; Susceptibility ; Metaanalysis ; Biology ; African Continental Ancestry Group ; Asian Continental Ancestry Group ; Blood Pressure ; Cells, Cultured ; Genome-Wide Association Study ; Humans ; Hypertension ; Microarray Analysis ; Polymorphism, Single Nucleotide ; Charge-Echogen Consortium ; Charge-Hf Consortium ; Wellcome Trust Case Control Consortium ; Developmental Biology ; 11 Medical And Health Sciences ; 06 Biological Sciences;
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creatorcontrib
0Georg B Ehret
1Teresa Ferreira
2Daniel I Chasman
3Anne U Jackson
4Ellen M Schmidt
5Toby Johnson
6Gudmar Thorleifsson
7Jian'An Luan
8Louise A Donnelly
9Stavroula Kanoni
10Ann-Kristin Petersen
11Vasyl Pihur
12Rona J Strawbridge
13Dmitry Shungin
14Maria F Hughes
15Osorio Meirelles
16Marika Kaakinen
17Nabila Bouatia-Naji
18Kati Kristiansson
19Sonia Shah
20Marcus E Kleber
21Xiuqing Guo
22Leo-Pekka Lyytikäinen
23Cristiano Fava
24Niclas Eriksson
25Ilja M Nolte
26Patrik K Magnusson
27Elias L Salfati
28Loukianos S Rallidis
29Elizabeth Theusch
30Andrew J P Smith
31Lasse Folkersen
32Kate Witkowska
33Tune H Pers
34Roby Joehanes
35Stuart K Kim
36Lazaros Lataniotis
37Rick Jansen
38Andrew D Johnson
39Helen Warren
40Young Jin Kim
41Wei Zhao
42Ying Wu
43Bamidele O Tayo
44Murielle Bochud
45Devin Absher
46Linda S Adair
47Najaf Amin
48Dan E Arking
49Tomas Axelsson
50Damiano Baldassarre
51Beverley Balkau
52Stefania Bandinelli
53Michael R Barnes
54Inês Barroso
55Stephen Bevan
56Joshua C Bis
57Gyda Bjornsdottir
58Michael Boehnke
59Eric Boerwinkle
60Lori L Bonnycastle
61Dorret I Boomsma
62Stefan R Bornstein
63Morris J Brown
64Michel Burnier
65Claudia P Cabrera
66John C Chambers
67I-Shou Chang
68Ching-Yu Cheng
69Peter S Chines
70Ren-Hua Chung
71Francis S Collins
72John M Connell
73Angela Döring
74Jean Dallongeville
75John Danesh
76Ulf De Faire
77Graciela Delgado
78Anna F Dominiczak
79Alex S F Doney
80Fotios Drenos
81Sarah Edkins
82John D Eicher
83Roberto Elosua
84Stefan Enroth
85Jeanette Erdmann
86Per Eriksson
87Tonu Esko
88Evangelos Evangelou
89Alun Evans
90Tove Fall
91Martin Farrall
92Janine F Felix
93Jean Ferrières
94Luigi Ferrucci
95Myriam Fornage
96Terrence Forrester
97Nora Franceschini
98Oscar H Franco
99Anders Franco-Cereceda
100...
titleThe genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
general
0Nature Publishing Group
110.1038/ng.3667
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recordidnature_a10.1038/ng.3667
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titleThe genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
authorGeorg B Ehret ; Teresa Ferreira ; Daniel I Chasman ; Anne U Jackson ; Ellen M Schmidt ; Toby Johnson ; Gudmar Thorleifsson ; Jian'An Luan ; Louise A Donnelly ; Stavroula Kanoni ; Ann-Kristin Petersen ; Vasyl Pihur ; Rona J Strawbridge ; Dmitry Shungin ; Maria F Hughes ; Osorio Meirelles ; Marika Kaakinen ; Nabila Bouatia-Naji ; Kati Kristiansson ; Sonia Shah ; Marcus E Kleber ; Xiuqing Guo ; Leo-Pekka Lyytikäinen ; Cristiano Fava ; Niclas Eriksson ; Ilja M Nolte ; Patrik K Magnusson ; Elias L Salfati ; Loukianos S Rallidis ; Elizabeth Theusch ; Andrew J P Smith ; Lasse Folkersen ; Kate Witkowska ; Tune H Pers ; Roby Joehanes ; Stuart K Kim ; Lazaros Lataniotis ; Rick Jansen ; Andrew D Johnson ; Helen Warren ; Young Jin Kim ; Wei Zhao ; Ying Wu ; Bamidele O Tayo ; Murielle Bochud ; Devin Absher ; Linda S Adair ; Najaf Amin ; Dan E Arking ; Tomas Axelsson ; Damiano Baldassarre ; Beverley Balkau ; Stefania Bandinelli ; Michael R Barnes ; Inês Barroso ; Stephen Bevan ; Joshua C Bis ; Gyda Bjornsdottir ; Michael Boehnke ; Eric Boerwinkle ; Lori L Bonnycastle ; Dorret I Boomsma ; Stefan R Bornstein ; Morris J Brown ; Michel Burnier ; Claudia P Cabrera ; John C Chambers ; I-Shou Chang ; Ching-Yu Cheng ; Peter S Chines ; Ren-Hua Chung ; Francis S Collins ; John M Connell ; Angela Döring ; Jean Dallongeville ; John Danesh ; Ulf De Faire ; Graciela Delgado ; Anna F Dominiczak ; Alex S F Doney ; Fotios Drenos ; Sarah Edkins ; John D Eicher ; Roberto Elosua ; Stefan Enroth ; Jeanette Erdmann ; Per Eriksson ; Tonu Esko ; Evangelos Evangelou ; Alun Evans ; Tove Fall ; Martin Farrall ; Janine F Felix ; Jean Ferrières ; Luigi Ferrucci ; Myriam Fornage ; Terrence Forrester ; Nora Franceschini ; Oscar H Franco ; Anders Franco-Cereceda ; Ross M Fraser ; Santhi K Ganesh ; He Gao ; Karl Gertow ; Francesco Gianfagna ; Bruna Gigante ; Franco Giulianini ; Anuj Goel ; Alison H Goodall ; Mark O Goodarzi ; Mathias Gorski ; Jürgen Gräßler ; Christopher J Groves ; Vilmundur Gudnason ; Ulf Gyllensten ; Göran Hallmans ; Anna-Liisa Hartikainen ; Maija Hassinen ; Aki S Havulinna ; Caroline Hayward ; Serge Hercberg ; Karl-Heinz Herzig ; Andrew A Hicks ; Aroon D Hingorani ; Joel N Hirschhorn ; Albert Hofman ; Jostein Holmen ; Oddgeir Lingaas Holmen ; Jouke-Jan Hottenga ; Phil Howard ; Chao A Hsiung ; Steven C Hunt ; M Arfan Ikram ; Thomas Illig ; Carlos Iribarren ; Richard A Jensen ; Mika Kähönen ; Hyun Min Kang ; Sekar Kathiresan ; Brendan J Keating ; Kay-Tee Khaw ; Yun Kyoung Kim ; Eric Kim ; Mika Kivimaki ; Norman Klopp ; Genovefa Kolovou ; Pirjo Komulainen ; Jaspal S Kooner ; Gulum Kosova ; Ronald M Krauss ; Diana Kuh ; Zoltan Kutalik ; Johanna Kuusisto ; Kirsti Kvaløy ; Timo A Lakka ; Nanette R Lee ; I-Te Lee ; Wen-Jane Lee ; Daniel Levy ; Xiaohui Li ; Kae-Woei Liang ; Honghuang Lin ; Li Lin ; Jaana Lindström ; Stéphane Lobbens ; Satu Männistö ; Gabriele Müller ; Martina Müller-Nurasyid ; François Mach ; Hugh S Markus ; Eirini Marouli ; Mark I Mccarthy ; Colin A Mckenzie ; Pierre Meneton ; Cristina Menni ; Andres Metspalu ; Vladan Mijatovic ; Leena Moilanen ; May E Montasser ; Andrew D Morris ; Alanna C Morrison ; Antonella Mulas ; Ramaiah Nagaraja ; Narisu Narisu ; Kjell Nikus ; Christopher J O'Donnell ; Paul F O'Reilly ; Ken K Ong ; Fred Paccaud ; Cameron D Palmer ; Afshin Parsa ; Nancy L Pedersen ; Brenda W Penninx ; Markus Perola ; Annette Peters ; Neil Poulter ; Peter P Pramstaller ; Bruce M Psaty ; Thomas Quertermous ; Dabeeru C Rao ; Asif Rasheed ; N William Rayner ; Frida Renström ; Rainer Rettig ; Kenneth M Rice ; Robert Roberts ; Lynda M Rose ; Jacques Rossouw ; Nilesh J Samani ; Serena Sanna ; Jouko Saramies ; Heribert Schunkert ; Sylvain Sebert ; Wayne H-H Sheu ; Young-Ah Shin ; Xueling Sim ; Johannes H Smit ; Albert V Smith ; Maria X Sosa ; Tim D Spector ; Alena Stančáková ; Alice V Stanton ; Kathleen E Stirrups ; Heather M Stringham ; Johan Sundstrom ; Amy J Swift ; Ann-Christine Syvänen ; E-Shyong Tai ; Toshiko Tanaka ; Kirill V Tarasov ; Alexander Teumer ; Unnur Thorsteinsdottir ; Martin D Tobin ; Elena Tremoli ; Andre G Uitterlinden ; Matti Uusitupa ; Ahmad Vaez ; Dhananjay Vaidya ; Cornelia M Van Duijn ; Erik P A Van Iperen ; Ramachandran S Vasan ; Germaine C Verwoert ; Jarmo Virtamo ; Veronique Vitart ; Benjamin F Voight ; Peter Vollenweider ; Aline Wagner ; Louise V Wain ; Nicholas J Wareham ; Hugh Watkins ; Alan B Weder ; Harm-Jan Westra ; Rainford Wilks ; Tom Wilsgaard ; James F Wilson ; Tien Y Wong ; Tsun-Po Yang ; Jie Yao ; Loic Yengo ; Weihua Zhang ; Jing Hua Zhao ; Xiaofeng Zhu ; Pascal Bovet ; Richard S Cooper ; Karen L Mohlke ; Danish Saleheen ; Jong-Young Lee ; Paul Elliott ; Hinco J Gierman ; Cristen J Willer ; Lude Franke ; G Kees Hovingh ; Kent D Taylor ; George Dedoussis ; Peter Sever ; Andrew Wong ; Lars Lind ; Themistocles L Assimes ; Inger Njølstad ; Peter E H Schwarz ; Claudia Langenberg ; Harold Snieder ; Mark J Caulfield ; Olle Melander ; Markku Laakso ; Juha Saltevo ; Rainer Rauramaa ; Jaakko Tuomilehto ; Erik Ingelsson ; Terho Lehtimäki ; Kristian Hveem ; Walter Palmas ; Winfried März ; Meena Kumari ; Veikko Salomaa ; Yii-Der I Chen ; Jerome I Rotter ; Philippe Froguel ; Marjo-Riitta Jarvelin ; Edward G Lakatta ; Kari Kuulasmaa ; Paul W Franks ; Anders Hamsten ; H-Erich Wichmann ; Colin N A Palmer ; Kari Stefansson ; Paul M Ridker ; Ruth J F Loos ; Aravinda Chakravarti ; Panos Deloukas ; Andrew P Morris ; Christopher Newton-Cheh ; Patricia B Munroe
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0Georg B Ehret
1Teresa Ferreira
2Daniel I Chasman
3Anne U Jackson
4Ellen M Schmidt
5Toby Johnson
6Gudmar Thorleifsson
7Jian'An Luan
8Louise A Donnelly
9Stavroula Kanoni
10Ann-Kristin Petersen
11Vasyl Pihur
12Rona J Strawbridge
13Dmitry Shungin
14Maria F Hughes
15Osorio Meirelles
16Marika Kaakinen
17Nabila Bouatia-Naji
18Kati Kristiansson
19Sonia Shah
20Marcus E Kleber
21Xiuqing Guo
22Leo-Pekka Lyytikäinen
23Cristiano Fava
24Niclas Eriksson
25Ilja M Nolte
26Patrik K Magnusson
27Elias L Salfati
28Loukianos S Rallidis
29Elizabeth Theusch
30Andrew J P Smith
31Lasse Folkersen
32Kate Witkowska
33Tune H Pers
34Roby Joehanes
35Stuart K Kim
36Lazaros Lataniotis
37Rick Jansen
38Andrew D Johnson
39Helen Warren
40Young Jin Kim
41Wei Zhao
42Ying Wu
43Bamidele O Tayo
44Murielle Bochud
45Devin Absher
46Linda S Adair
47Najaf Amin
48Dan E Arking
49Tomas Axelsson
50Damiano Baldassarre
51Beverley Balkau
52Stefania Bandinelli
53Michael R Barnes
54Inês Barroso
55Stephen Bevan
56Joshua C Bis
57Gyda Bjornsdottir
58Michael Boehnke
59Eric Boerwinkle
60Lori L Bonnycastle
61Dorret I Boomsma
62Stefan R Bornstein
63Morris J Brown
64Michel Burnier
65Claudia P Cabrera
66John C Chambers
67I-Shou Chang
68Ching-Yu Cheng
69Peter S Chines
70Ren-Hua Chung
71Francis S Collins
72John M Connell
73Angela Döring
74Jean Dallongeville
75John Danesh
76Ulf De Faire
77Graciela Delgado
78Anna F Dominiczak
79Alex S F Doney
80Fotios Drenos
81Sarah Edkins
82John D Eicher
83Roberto Elosua
84Stefan Enroth
85Jeanette Erdmann
86Per Eriksson
87Tonu Esko
88Evangelos Evangelou
89Alun Evans
90Tove Fall
91Martin Farrall
92Janine F Felix
93Jean Ferrières
94Luigi Ferrucci
95Myriam Fornage
96Terrence Forrester
97Nora Franceschini
98Oscar H Franco
99Anders Franco-Cereceda
100...
jtitleNature Genetics
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au
0Georg B Ehret
1Teresa Ferreira
2Daniel I Chasman
3Anne U Jackson
4Ellen M Schmidt
5Toby Johnson
6Gudmar Thorleifsson
7Jian'An Luan
8Louise A Donnelly
9Stavroula Kanoni
10Ann-Kristin Petersen
11Vasyl Pihur
12Rona J Strawbridge
13Dmitry Shungin
14Maria F Hughes
15Osorio Meirelles
16Marika Kaakinen
17Nabila Bouatia-Naji
18Kati Kristiansson
19Sonia Shah
20Marcus E Kleber
21Xiuqing Guo
22Leo-Pekka Lyytikäinen
23Cristiano Fava
24Niclas Eriksson
25Ilja M Nolte
26Patrik K Magnusson
27Elias L Salfati
28Loukianos S Rallidis
29Elizabeth Theusch
30Andrew J P Smith
31Lasse Folkersen
32Kate Witkowska
33Tune H Pers
34Roby Joehanes
35Stuart K Kim
36Lazaros Lataniotis
37Rick Jansen
38Andrew D Johnson
39Helen Warren
40Young Jin Kim
41Wei Zhao
42Ying Wu
43Bamidele O Tayo
44Murielle Bochud
45Devin Absher
46Linda S Adair
47Najaf Amin
48Dan E Arking
49Tomas Axelsson
50Damiano Baldassarre
51Beverley Balkau
52Stefania Bandinelli
53Michael R Barnes
54Inês Barroso
55Stephen Bevan
56Joshua C Bis
57Gyda Bjornsdottir
58Michael Boehnke
59Eric Boerwinkle
60Lori L Bonnycastle
61Dorret I Boomsma
62Stefan R Bornstein
63Morris J Brown
64Michel Burnier
65Claudia P Cabrera
66John C Chambers
67I-Shou Chang
68Ching-Yu Cheng
69Peter S Chines
70Ren-Hua Chung
71Francis S Collins
72John M Connell
73Angela Döring
74Jean Dallongeville
75John Danesh
76Ulf De Faire
77Graciela Delgado
78Anna F Dominiczak
79Alex S F Doney
80Fotios Drenos
81Sarah Edkins
82John D Eicher
83Roberto Elosua
84Stefan Enroth
85Jeanette Erdmann
86Per Eriksson
87Tonu Esko
88Evangelos Evangelou
89Alun Evans
90Tove Fall
91Martin Farrall
92Janine F Felix
93Jean Ferrières
94Luigi Ferrucci
95Myriam Fornage
96Terrence Forrester
97Nora Franceschini
98Oscar H Franco
99Anders Franco-Cereceda
100...
atitleThe genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
jtitleNature Genetics
risdate20160912
issn1061-4036
eissn1546-1718
genrearticle
ristypeJOUR
pubNature Publishing Group
doi10.1038/ng.3667
orcidid0000-0003-0663-7275
issue10
volume48
pages1171-1184
date2016-09-12