Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.

Authors:
Dr Anubha Mahajan, PhD
Dr Anubha Mahajan, PhD
Wellcome Trust Centre for Human Genetics, University of Oxford
UK
Dr Eirini Marouli
Dr Eirini Marouli
School of Health Science and Education
Praveen Surendran Fotios Drenos Robin Young Helen Warren James P Cook Alisa K Manning Niels Grarup Xueling Sim Daniel R Barnes Kate Witkowska James R Staley Vinicius Tragante Taru Tukiainen Hanieh Yaghootkar Nicholas Masca Daniel F Freitag Teresa Ferreira Olga Giannakopoulou Andrew Tinker Magdalena Harakalova Evelin Mihailov Chunyu Liu Aldi T Kraja Sune Fallgaard Nielsen Asif Rasheed Maria Samuel Wei Zhao Lori L Bonnycastle Anne U Jackson Narisu Narisu Amy J Swift Lorraine Southam Jonathan Marten Jeroen R Huyghe Alena Stančáková Cristiano Fava Therese Ohlsson Angela Matchan Kathleen E Stirrups Jette Bork-Jensen Anette P Gjesing Jukka Kontto Markus Perola Susan Shaw-Hawkins Aki S Havulinna He Zhang Louise A Donnelly Christopher J Groves N William Rayner Matt J Neville Neil R Robertson Andrianos M Yiorkas Karl-Heinz Herzig Eero Kajantie Weihua Zhang Sara M Willems Lars Lannfelt Giovanni Malerba Nicole Soranzo Elisabetta Trabetti Niek Verweij Evangelos Evangelou Alireza Moayyeri Anne-Claire Vergnaud Christopher P Nelson Alaitz Poveda Tibor V Varga Muriel Caslake Anton Jm de Craen Stella Trompet Jian'an Luan Robert A Scott Sarah E Harris David Cm Liewald Riccardo Marioni Cristina Menni Aliki-Eleni Farmaki Göran Hallmans Frida Renström Jennifer E Huffman Maija Hassinen Stephen Burgess Ramachandran S Vasan Janine F Felix Maria Uria-Nickelsen Anders Malarstig Dermot F Reily Maarten Hoek Thomas Vogt Honghuang Lin Wolfgang Lieb Matthew Traylor Hugh F Markus Heather M Highland Anne E Justice Jaana Lindström Matti Uusitupa Pirjo Komulainen Timo A Lakka Rainer Rauramaa Ozren Polasek Igor Rudan Olov Rolandsson Paul W Franks George Dedoussis Timothy D Spector Pekka Jousilahti Satu Männistö Ian J Deary John M Starr Claudia Langenberg Nick J Wareham Morris J Brown Anna F Dominiczak John M Connell J Wouter Jukema Naveed Sattar Ian Ford Chris J Packard Tõnu Esko Reedik Mägi Andres Metspalu Rudolf A de Boer Peter van der Meer Pim van der Harst Giovanni Gambaro Erik Ingelsson Lars Lind Paul Iw de Bakker Mattijs E Numans Ivan Brandslund Cramer Christensen Eva Rb Petersen Eeva Korpi-Hyövälti Heikki Oksa John C Chambers Jaspal S Kooner Alexandra If Blakemore Steve Franks Marjo-Riitta Jarvelin Lise L Husemoen Allan Linneberg Tea Skaaby Betina Thuesen Fredrik Karpe Jaakko Tuomilehto Alex Sf Doney Andrew D Morris Colin Na Palmer Oddgeir Lingaas Holmen Kristian Hveem Cristen J Willer Tiinamaija Tuomi Leif Groop AnneMari Käräjämäki Aarno Palotie Samuli Ripatti Veikko Salomaa Dewan S Alam Abdulla Al Shafi Majumder Emanuele Di Angelantonio Rajiv Chowdhury Mark I McCarthy Neil Poulter Alice V Stanton Peter Sever Philippe Amouyel Dominique Arveiler Stefan Blankenberg Jean Ferrières Frank Kee Kari Kuulasmaa Martina Müller-Nurasyid Giovanni Veronesi Jarmo Virtamo Panos Deloukas Paul Elliott Eleftheria Zeggini Sekar Kathiresan Olle Melander Johanna Kuusisto Markku Laakso Sandosh Padmanabhan David Porteous Caroline Hayward Generation Scotland Francis S Collins Karen L Mohlke Torben Hansen Oluf Pedersen Michael Boehnke Heather M Stringham Philippe Frossard Christopher Newton-Cheh Martin D Tobin Børge Grønne Nordestgaard Mark J Caulfield Andrew P Morris Maciej Tomaszewski Nilesh J Samani Danish Saleheen Folkert W Asselbergs Cecilia M Lindgren John Danesh Louise V Wain Adam S Butterworth Joanna Mm Howson Patricia B Munroe

Nat Genet 2016 10 12;48(10):1151-1161. Epub 2016 Sep 12.

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

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5056636PMC
http://dx.doi.org/10.1038/ng.3654DOI Listing
October 2016
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