The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
Nature Genetics2016Vol. 48(10), pp. 1171–1184
Citations Over TimeTop 1% of 2016 papers
Georg Ehret, Teresa Ferreira, Daniel I. Chasman, Anne Jackson, Ellen M. Schmidt, Toby Johnson, Guðmar Þorleifsson, Jian’an Luan, Lousie A Donnelly, Stavroula Kanoni, Ann-Kristin Petersen, Vasyl Pihur, Rona J. Strawbridge, Dmitry Shungin, Maria 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. E. Magnusson, Elias Salfati, Lοukianos S. Rallidis, Elizabeth Theusch, Andrew J. Smith, Lasse Folkersen, Kate Witkowska, Tune H. Pers, Roby Joehanes, Stuart K. Kim, Lazaros Lataniotis, Rick Jansen, Andrew D. Johnson, Helen R. 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, Steve Bevan, Joshua C. 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Tarasov, Alexander Teumer, Unnur Thorsteinsdottir, Martin D. Tobin, Elena Tremoli, André 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, Véronique Vitart, Benjamin F. Voight, Péter 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 Yin Wong, Tsun-Po Yang, Jie Yao, Loïc Yengo, Weihua Zhang, Jing Hua Zhao, Xiaofeng Zhu, Pascal Bovet, Stephen S. Rich, Karen L Mohlke, Danish Saleheen, Jong‐Young Lee, Paul Elliott, Hinco J. Gierman, Cristen J. Willer, Lude Franke, G. Kees Hovingh, Kent D. Taylor, George Dedoussis, Peter S. Sever, Andrew Wong, Lars Lind, Themistocles L. Assimes, Inger Njølstad, Peter E. H. 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 Järvelin, Edward G. Lakatta, Kari Kuulasmaa, Paul W. Franks, Anders Hamsten, H-Erich Wichmann, Colin N A Palmer, Kāri Stefánsson, Paul M. Ridker, Ruth J. F. Loos, Aravinda Chakravarti, Panos Deloukas, Andrew P. Morris, Christopher Newton‐Cheh, Patricia B. Munroe
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.
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