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


ABSTRACT: 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.

SUBMITTER: Ehret GB 

PROVIDER: S-EPMC5042863 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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

Ehret Georg B GB   Ferreira Teresa T   Chasman Daniel I DI   Jackson Anne U AU   Schmidt Ellen M EM   Johnson Toby T   Thorleifsson Gudmar G   Luan Jian'an J   Donnelly Lousie A LA   Kanoni Stavroula S   Petersen Ann-Kristin AK   Pihur Vasyl V   Strawbridge Rona J RJ   Shungin Dmitry D   Hughes Maria F MF   Meirelles Osorio O   Kaakinen Marika M   Bouatia-Naji Nabila N   Kristiansson Kati K   Shah Sonia S   Kleber Marcus E ME   Guo Xiuqing X   Lyytikäinen Leo-Pekka LP   Fava Cristiano C   Eriksson Niclas N   Nolte Ilja M IM   Magnusson Patrik K PK   Salfati Elias L EL   Rallidis Loukianos S LS   Theusch Elizabeth E   Smith Andrew J P AJP   Folkersen Lasse L   Witkowska Kate K   Pers Tune H TH   Joehanes Roby R   Kim Stuart K SK   Lataniotis Lazaros L   Jansen Rick R   Johnson Andrew D AD   Warren Helen H   Kim Young Jin YJ   Zhao Wei W   Wu Ying Y   Tayo Bamidele O BO   Bochud Murielle M   Absher Devin D   Adair Linda S LS   Amin Najaf N   Arking Dan E DE   Axelsson Tomas T   Baldassarre Damiano D   Balkau Beverley B   Bandinelli Stefania S   Barnes Michael R MR   Barroso Inês I   Bevan Stephen S   Bis Joshua C JC   Bjornsdottir Gyda G   Boehnke Michael M   Boerwinkle Eric E   Bonnycastle Lori L LL   Boomsma Dorret I DI   Bornstein Stefan R SR   Brown Morris J MJ   Burnier Michel M   Cabrera Claudia P CP   Chambers John C JC   Chang I-Shou IS   Cheng Ching-Yu CY   Chines Peter S PS   Chung Ren-Hua RH   Collins Francis S FS   Connell John M JM   Döring Angela A   Dallongeville Jean J   Danesh John J   de Faire Ulf U   Delgado Graciela G   Dominiczak Anna F AF   Doney Alex S F ASF   Drenos Fotios F   Edkins Sarah S   Eicher John D JD   Elosua Roberto R   Enroth Stefan S   Erdmann Jeanette J   Eriksson Per P   Esko Tonu T   Evangelou Evangelos E   Evans Alun A   Fall Tove T   Farrall Martin M   Felix Janine F JF   Ferrières Jean J   Ferrucci Luigi L   Fornage Myriam M   Forrester Terrence T   Franceschini Nora N   Duran Oscar H Franco OHF   Franco-Cereceda Anders A   Fraser Ross M RM   Ganesh Santhi K SK   Gao He H   Gertow Karl K   Gianfagna Francesco F   Gigante Bruna B   Giulianini Franco F   Goel Anuj A   Goodall Alison H AH   Goodarzi Mark O MO   Gorski Mathias M   Gräßler Jürgen J   Groves Christopher C   Gudnason Vilmundur V   Gyllensten Ulf U   Hallmans Göran G   Hartikainen Anna-Liisa AL   Hassinen Maija M   Havulinna Aki S AS   Hayward Caroline C   Hercberg Serge S   Herzig Karl-Heinz KH   Hicks Andrew A AA   Hingorani Aroon D AD   Hirschhorn Joel N JN   Hofman Albert A   Holmen Jostein J   Holmen Oddgeir Lingaas OL   Hottenga Jouke-Jan JJ   Howard Phil P   Hsiung Chao A CA   Hunt Steven C SC   Ikram M Arfan MA   Illig Thomas T   Iribarren Carlos C   Jensen Richard A RA   Kähönen Mika M   Kang Hyun H   Kathiresan Sekar S   Keating Brendan J BJ   Khaw Kay-Tee KT   Kim Yun Kyoung YK   Kim Eric E   Kivimaki Mika M   Klopp Norman N   Kolovou Genovefa G   Komulainen Pirjo P   Kooner Jaspal S JS   Kosova Gulum G   Krauss Ronald M RM   Kuh Diana D   Kutalik Zoltan Z   Kuusisto Johanna J   Kvaløy Kirsti K   Lakka Timo A TA   Lee Nanette R NR   Lee I-Te IT   Lee Wen-Jane WJ   Levy Daniel D   Li Xiaohui X   Liang Kae-Woei KW   Lin Honghuang H   Lin Li L   Lindström Jaana J   Lobbens Stéphane S   Männistö Satu S   Müller Gabriele G   Müller-Nurasyid Martina M   Mach François F   Markus Hugh S HS   Marouli Eirini E   McCarthy Mark I MI   McKenzie Colin A CA   Meneton Pierre P   Menni Cristina C   Metspalu Andres A   Mijatovic Vladan V   Moilanen Leena L   Montasser May E ME   Morris Andrew D AD   Morrison Alanna C AC   Mulas Antonella A   Nagaraja Ramaiah R   Narisu Narisu N   Nikus Kjell K   O'Donnell Christopher J CJ   O'Reilly Paul F PF   Ong Ken K KK   Paccaud Fred F   Palmer Cameron D CD   Parsa Afshin A   Pedersen Nancy L NL   Penninx Brenda W BW   Perola Markus M   Peters Annette A   Poulter Neil N   Pramstaller Peter P PP   Psaty Bruce M BM   Quertermous Thomas T   Rao Dabeeru C DC   Rasheed Asif A   Rayner N William N W R NWNWR   Renström Frida F   Rettig Rainer R   Rice Kenneth M KM   Roberts Robert R   Rose Lynda M LM   Rossouw Jacques J   Samani Nilesh J NJ   Sanna Serena S   Saramies Jouko J   Schunkert Heribert H   Sebert Sylvain S   Sheu Wayne H-H WH   Shin Young-Ah YA   Sim Xueling X   Smit Johannes H JH   Smith Albert V AV   Sosa Maria X MX   Spector Tim D TD   Stančáková Alena A   Stanton Alice A   Stirrups Kathleen E KE   Stringham Heather M HM   Sundstrom Johan J   Swift Amy J AJ   Syvänen Ann-Christine AC   Tai E-Shyong ES   Tanaka Toshiko T   Tarasov Kirill V KV   Teumer Alexander A   Thorsteinsdottir Unnur U   Tobin Martin D MD   Tremoli Elena E   Uitterlinden Andre G AG   Uusitupa Matti M   Vaez Ahmad A   Vaidya Dhananjay D   van Duijn Cornelia M CM   van Iperen Erik P A EPA   Vasan Ramachandran S RS   Verwoert Germaine C GC   Virtamo Jarmo J   Vitart Veronique V   Voight Benjamin F BF   Vollenweider Peter P   Wagner Aline A   Wain Louise V LV   Wareham Nicholas J NJ   Watkins Hugh H   Weder Alan B AB   Westra Harm-Jan HJ   Wilks Rainford R   Wilsgaard Tom T   Wilson James F JF   Wong Tien Y TY   Yang Tsun-Po TP   Yao Jie J   Yengo Loic L   Zhang Weihua W   Zhao Jing Hua JH   Zhu Xiaofeng X   Bovet Pascal P   Cooper Richard S RS   Mohlke Karen L KL   Saleheen Danish D   Lee Jong-Young JY   Elliott Paul P   Gierman Hinco J HJ   Willer Cristen J CJ   Franke Lude L   Hovingh G Kees GK   Taylor Kent D KD   Dedoussis George G   Sever Peter P   Wong Andrew A   Lind Lars L   Assimes Themistocles L TL   Njølstad Inger I   Schwarz Peter Eh PE   Langenberg Claudia C   Snieder Harold H   Caulfield Mark J MJ   Melander Olle O   Laakso Markku M   Saltevo Juha J   Rauramaa Rainer R   Tuomilehto Jaakko J   Ingelsson Erik E   Lehtimäki Terho T   Hveem Kristian K   Palmas Walter W   März Winfried W   Kumari Meena M   Salomaa Veikko V   Chen Yii-Der I YI   Rotter Jerome I JI   Froguel Philippe P   Jarvelin Marjo-Riitta MR   Lakatta Edward G EG   Kuulasmaa Kari K   Franks Paul W PW   Hamsten Anders A   Wichmann H-Erich HE   Palmer Colin N A CNA   Stefansson Kari K   Ridker Paul M PM   Loos Ruth J F RJF   Chakravarti Aravinda A   Deloukas Panos P   Morris Andrew P AP   Newton-Cheh Christopher C   Munroe Patricia B PB  

Nature genetics 20160912 10


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 endotheli  ...[more]

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