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

Authors:
Dr. Elizabeth Theusch, PhD
Dr. Elizabeth Theusch, PhD
Children's Hospital Oakland Research Institute
CA | USA
Dr. Hinco J Gierman, PhD
Dr. Hinco J Gierman, PhD
illumina
Senior Manager Scientific & Translational Software
CA | United States
Dr Eirini Marouli
Dr Eirini Marouli
School of Health Science and Education
Georg B Ehret Teresa Ferreira Daniel I Chasman Anne U Jackson Ellen M Schmidt Toby Johnson Gudmar Thorleifsson Jian'an Luan Lousie 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 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 Duran 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 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 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 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 N W R 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 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 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 Eh 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

Nat Genet 2016 10 12;48(10):1171-1184. Epub 2016 Sep 12.

Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, EC1M 6BQ, UK.

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.

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http://dx.doi.org/10.1038/ng.3667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042863PMC

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October 2016
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