利用全基因组关联研究以及血液和肾脏的表达数据集发现新型血压基因座和基因
Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.
作者信息
Wain Louise V, Vaez Ahmad, Jansen Rick, Joehanes Roby, van der Most Peter J, Erzurumluoglu A Mesut, O'Reilly Paul F, Cabrera Claudia P, Warren Helen R, Rose Lynda M, Verwoert Germaine C, Hottenga Jouke-Jan, Strawbridge Rona J, Esko Tonu, Arking Dan E, Hwang Shih-Jen, Guo Xiuqing, Kutalik Zoltan, Trompet Stella, Shrine Nick, Teumer Alexander, Ried Janina S, Bis Joshua C, Smith Albert V, Amin Najaf, Nolte Ilja M, Lyytikäinen Leo-Pekka, Mahajan Anubha, Wareham Nicholas J, Hofer Edith, Joshi Peter K, Kristiansson Kati, Traglia Michela, Havulinna Aki S, Goel Anuj, Nalls Mike A, Sõber Siim, Vuckovic Dragana, Luan Jian'an, Del Greco M Fabiola, Ayers Kristin L, Marrugat Jaume, Ruggiero Daniela, Lopez Lorna M, Niiranen Teemu, Enroth Stefan, Jackson Anne U, Nelson Christopher P, Huffman Jennifer E, Zhang Weihua, Marten Jonathan, Gandin Ilaria, Harris Sarah E, Zemunik Tatijana, Lu Yingchang, Evangelou Evangelos, Shah Nabi, de Borst Martin H, Mangino Massimo, Prins Bram P, Campbell Archie, Li-Gao Ruifang, Chauhan Ganesh, Oldmeadow Christopher, Abecasis Gonçalo, Abedi Maryam, Barbieri Caterina M, Barnes Michael R, Batini Chiara, Beilby John, Blake Tineka, Boehnke Michael, Bottinger Erwin P, Braund Peter S, Brown Morris, Brumat Marco, Campbell Harry, Chambers John C, Cocca Massimiliano, Collins Francis, Connell John, Cordell Heather J, Damman Jeffrey J, Davies Gail, de Geus Eco J, de Mutsert Renée, Deelen Joris, Demirkale Yusuf, Doney Alex S F, Dörr Marcus, Farrall Martin, Ferreira Teresa, Frånberg Mattias, Gao He, Giedraitis Vilmantas, Gieger Christian, Giulianini Franco, Gow Alan J, Hamsten Anders, Harris Tamara B, Hofman Albert, Holliday Elizabeth G, Hui Jennie, Jarvelin Marjo-Riitta, Johansson Åsa, Johnson Andrew D, Jousilahti Pekka, Jula Antti, Kähönen Mika, Kathiresan Sekar, Khaw Kay-Tee, Kolcic Ivana, Koskinen Seppo, Langenberg Claudia, Larson Marty, Launer Lenore J, Lehne Benjamin, Liewald David C M, Lin Li, Lind Lars, Mach François, Mamasoula Chrysovalanto, Menni Cristina, Mifsud Borbala, Milaneschi Yuri, Morgan Anna, Morris Andrew D, Morrison Alanna C, Munson Peter J, Nandakumar Priyanka, Nguyen Quang Tri, Nutile Teresa, Oldehinkel Albertine J, Oostra Ben A, Org Elin, Padmanabhan Sandosh, Palotie Aarno, Paré Guillaume, Pattie Alison, Penninx Brenda W J H, Poulter Neil, Pramstaller Peter P, Raitakari Olli T, Ren Meixia, Rice Kenneth, Ridker Paul M, Riese Harriëtte, Ripatti Samuli, Robino Antonietta, Rotter Jerome I, Rudan Igor, Saba Yasaman, Saint Pierre Aude, Sala Cinzia F, Sarin Antti-Pekka, Schmidt Reinhold, Scott Rodney, Seelen Marc A, Shields Denis C, Siscovick David, Sorice Rossella, Stanton Alice, Stott David J, Sundström Johan, Swertz Morris, Taylor Kent D, Thom Simon, Tzoulaki Ioanna, Tzourio Christophe, Uitterlinden André G, Völker Uwe, Vollenweider Peter, Wild Sarah, Willemsen Gonneke, Wright Alan F, Yao Jie, Thériault Sébastien, Conen David, Attia John, Sever Peter, Debette Stéphanie, Mook-Kanamori Dennis O, Zeggini Eleftheria, Spector Tim D, van der Harst Pim, Palmer Colin N A, Vergnaud Anne-Claire, Loos Ruth J F, Polasek Ozren, Starr John M, Girotto Giorgia, Hayward Caroline, Kooner Jaspal S, Lindgren Cecila M, Vitart Veronique, Samani Nilesh J, Tuomilehto Jaakko, Gyllensten Ulf, Knekt Paul, Deary Ian J, Ciullo Marina, Elosua Roberto, Keavney Bernard D, Hicks Andrew A, Scott Robert A, Gasparini Paolo, Laan Maris, Liu YongMei, Watkins Hugh, Hartman Catharina A, Salomaa Veikko, Toniolo Daniela, Perola Markus, Wilson James F, Schmidt Helena, Zhao Jing Hua, Lehtimäki Terho, van Duijn Cornelia M, Gudnason Vilmundur, Psaty Bruce M, Peters Annette, Rettig Rainer, James Alan, Jukema J Wouter, Strachan David P, Palmas Walter, Metspalu Andres, Ingelsson Erik, Boomsma Dorret I, Franco Oscar H, Bochud Murielle, Newton-Cheh Christopher, Munroe Patricia B, Elliott Paul, Chasman Daniel I, Chakravarti Aravinda, Knight Joanne, Morris Andrew P, Levy Daniel, Tobin Martin D, Snieder Harold, Caulfield Mark J, Ehret Georg B
机构信息
From the Department of Health Sciences (L.V.W., A.M.E., N. Shrine, C.B., T.B., M.D.T.), University of Leicester, United Kingdom.
Department of Epidemiology (A.V., P.J.v.d.M., I.M.N., H. Snieder), University of Groningen, University Medical Center Groningen, The Netherlands.
出版信息
Hypertension. 2017 Sep;70(3):e4-e19. doi: 10.1161/HYPERTENSIONAHA.117.09438. Epub 2017 Jul 24.
Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near , , , , , and , and provide new replication evidence for a further 2 signals in and . Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
血压升高是心血管疾病的主要危险因素，且有很大的遗传因素影响。影响血压的基因变异有可能识别出治疗高血压的新药物靶点。为了发现更多新的血压相关基因座，我们在150134名欧洲血统个体中使用了基于千人基因组计划的基因填充，并在另外228245名个体中寻求独立复制的显著证据。我们报告了在、、、、和或其附近的6个新的关联信号，并为和中的另外2个信号提供了新的复制证据。结合总计12607名个体的大型全血基因表达资源，我们研究了所有新的和先前报道的信号，并确定了48个有证据表明参与血压调节且在多个资源中具有显著性的基因。还检测到了3个新的肾脏特异性信号。这些有力地涉及到的基因可能为治疗创新提供新的线索。
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