跨血统荟萃分析确定了与血压和高血压相关的罕见和常见变异。
Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.
作者信息
Surendran Praveen, Drenos Fotios, Young Robin, Warren Helen, Cook James P, Manning Alisa K, Grarup Niels, Sim Xueling, Barnes Daniel R, Witkowska Kate, Staley James R, Tragante Vinicius, Tukiainen Taru, Yaghootkar Hanieh, Masca Nicholas, Freitag Daniel F, Ferreira Teresa, Giannakopoulou Olga, Tinker Andrew, Harakalova Magdalena, Mihailov Evelin, Liu Chunyu, Kraja Aldi T, Fallgaard Nielsen Sune, Rasheed Asif, Samuel Maria, Zhao Wei, Bonnycastle Lori L, Jackson Anne U, Narisu Narisu, Swift Amy J, Southam Lorraine, Marten Jonathan, Huyghe Jeroen R, Stančáková Alena, Fava Cristiano, Ohlsson Therese, Matchan Angela, Stirrups Kathleen E, Bork-Jensen Jette, Gjesing Anette P, Kontto Jukka, Perola Markus, Shaw-Hawkins Susan, Havulinna Aki S, Zhang He, Donnelly Louise A, Groves Christopher J, Rayner N William, Neville Matt J, Robertson Neil R, Yiorkas Andrianos M, Herzig Karl-Heinz, Kajantie Eero, Zhang Weihua, Willems Sara M, Lannfelt Lars, Malerba Giovanni, Soranzo Nicole, Trabetti Elisabetta, Verweij Niek, Evangelou Evangelos, Moayyeri Alireza, Vergnaud Anne-Claire, Nelson Christopher P, Poveda Alaitz, Varga Tibor V, Caslake Muriel, de Craen Anton Jm, Trompet Stella, Luan Jian'an, Scott Robert A, Harris Sarah E, Liewald David Cm, Marioni Riccardo, Menni Cristina, Farmaki Aliki-Eleni, Hallmans Göran, Renström Frida, Huffman Jennifer E, Hassinen Maija, Burgess Stephen, Vasan Ramachandran S, Felix Janine F, Uria-Nickelsen Maria, Malarstig Anders, Reily Dermot F, Hoek Maarten, Vogt Thomas, Lin Honghuang, Lieb Wolfgang, Traylor Matthew, Markus Hugh F, Highland Heather M, Justice Anne E, Marouli Eirini, Lindström Jaana, Uusitupa Matti, Komulainen Pirjo, Lakka Timo A, Rauramaa Rainer, Polasek Ozren, Rudan Igor, Rolandsson Olov, Franks Paul W, Dedoussis George, Spector Timothy D, Jousilahti Pekka, Männistö Satu, Deary Ian J, Starr John M, Langenberg Claudia, Wareham Nick J, Brown Morris J, Dominiczak Anna F, Connell John M, Jukema J Wouter, Sattar Naveed, Ford Ian, Packard Chris J, Esko Tõnu, Mägi Reedik, Metspalu Andres, de Boer Rudolf A, van der Meer Peter, van der Harst Pim, Gambaro Giovanni, Ingelsson Erik, Lind Lars, de Bakker Paul Iw, Numans Mattijs E, Brandslund Ivan, Christensen Cramer, Petersen Eva Rb, Korpi-Hyövälti Eeva, Oksa Heikki, Chambers John C, Kooner Jaspal S, Blakemore Alexandra If, Franks Steve, Jarvelin Marjo-Riitta, Husemoen Lise L, Linneberg Allan, Skaaby Tea, Thuesen Betina, Karpe Fredrik, Tuomilehto Jaakko, Doney Alex Sf, Morris Andrew D, Palmer Colin Na, Holmen Oddgeir Lingaas, Hveem Kristian, Willer Cristen J, Tuomi Tiinamaija, Groop Leif, Käräjämäki AnneMari, Palotie Aarno, Ripatti Samuli, Salomaa Veikko, Alam Dewan S, Shafi Majumder Abdulla Al, Di Angelantonio Emanuele, Chowdhury Rajiv, McCarthy Mark I, Poulter Neil, Stanton Alice V, Sever Peter, Amouyel Philippe, Arveiler Dominique, Blankenberg Stefan, Ferrières Jean, Kee Frank, Kuulasmaa Kari, Müller-Nurasyid Martina, Veronesi Giovanni, Virtamo Jarmo, Deloukas Panos, Elliott Paul, Zeggini Eleftheria, Kathiresan Sekar, Melander Olle, Kuusisto Johanna, Laakso Markku, Padmanabhan Sandosh, Porteous David, Hayward Caroline, Scotland Generation, Collins Francis S, Mohlke Karen L, Hansen Torben, Pedersen Oluf, Boehnke Michael, Stringham Heather M, Frossard Philippe, Newton-Cheh Christopher, Tobin Martin D, Nordestgaard Børge Grønne, Caulfield Mark J, Mahajan Anubha, Morris Andrew P, Tomaszewski Maciej, Samani Nilesh J, Saleheen Danish, Asselbergs Folkert W, Lindgren Cecilia M, Danesh John, Wain Louise V, Butterworth Adam S, Howson Joanna Mm, Munroe Patricia B
机构信息
Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.
出版信息
Nat Genet. 2016 Oct;48(10):1151-1161. doi: 10.1038/ng.3654. Epub 2016 Sep 12.
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.
高血压是心血管疾病和过早死亡的主要风险因素。然而，对于特定的致病基因和途径的了解有限。为了更好地理解血压的遗传学，我们对多达192,763名个体中的242,296个罕见、低频和常见基因变异进行了基因分型，并使用约155,063个样本进行独立验证。我们在普通人群中鉴定出30个新的与血压或高血压相关的基因区域，包括RBM47、COL21A1和RRAS中的3个罕见错义变异，其效应比常见变异更大（>1.5 mmHg/等位基因）。在A2ML1中发现了多个罕见的无义变异和错义变异关联，并鉴定出ENPEP中的一个低频无义变异。我们的数据扩展了血压性状和高血压潜在的等位基因变异谱，为高血压的病理生理学提供了新的见解，并指出了临床干预的新靶点。
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