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

• Published in: Nature genetics Vol. 48; no. 10; pp. 1171 - 1184
• Main Authors: Chasman, Daniel I, Jackson, Anne U, Johnson, Toby, Thorleifsson, Gudmar, Luan, Jian'an, Pihur, Vasyl, Meirelles, Osorio, Bouatia-Naji, Nabila, Shah, Sonia, Nolte, Ilja M, Magnusson, Patrik K, Folkersen, Lasse, Kim, Young Jin, Zhao, Wei, Bochud, Murielle, Baldassarre, Damiano, Barroso, Inês, Chang, I-Shou, Chines, Peter S, Connell, John M, Döring, Angela, Dominiczak, Anna F, Doney, Alex S F, Erdmann, Jeanette, Eriksson, Per, Evangelou, Evangelos, Evans, Alun, Felix, Janine F, Gertow, Karl, Goodarzi, Mark O, Gorski, Mathias, Groves, Christopher J, Gyllensten, Ulf, Hallmans, Göran, Hercberg, Serge, Hicks, Andrew A, Hsiung, Chao A, Kang, Hyun Min, Kathiresan, Sekar, Khaw, Kay-Tee, Kim, Yun Kyoung, Klopp, Norman, Kolovou, Genovefa, Kooner, Jaspal S, Kosova, Gulum, Kutalik, Zoltan, Lee, I-Te, Lee, Wen-Jane, Lindström, Jaana, Lobbens, Stéphane, Männistö, Satu, Mach, François, Marouli, Eirini, McKenzie, Colin A, Menni, Cristina, Morris, Andrew D, Nagaraja, Ramaiah, Nikus, Kjell, O'Reilly, Paul F, Ong, Ken K, Parsa, Afshin, Penninx, Brenda W, Rossouw, Jacques, Saramies, Jouko, Shin, Young-Ah, Stanton, Alice V, Sundstrom, Johan, Syvänen, Ann-Christine, Tarasov, Kirill V, Thorsteinsdottir, Unnur, Uitterlinden, Andre G, Vaez, Ahmad, van Iperen, Erik P A, Vasan, Ramachandran S, Verwoert, Germaine C, Wain, Louise V, Watkins, Hugh, Westra, Harm-Jan, Wilks, Rainford, Wilsgaard, Tom, Yang, Tsun-Po, Yengo, Loic, Bovet, Pascal, Cooper, Richard S, Elliott, Paul, Willer, Cristen J, Lind, Lars, Assimes, Themistocles L, Snieder, Harold, Melander, Olle, Laakso, Markku, Rauramaa, Rainer, Ingelsson, Erik, Hveem, Kristian, Kumari, Meena, Rotter, Jerome I, Lakatta, Edward G, Palmer, Colin N A, Chakravarti, Aravinda, Deloukas, Panos
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2016; Nature Publishing Group
• Subjects: 45/43; 631/208/205/2138; 692/699/75/243; Agriculture; Analysis; Animal Genetics and Genomics; Asian People - genetics; Basic Medicine; Biomedicine; Black People - genetics; Blood pressure; Blood Pressure - genetics; Blood pressure regulation; Cancer Research; Cells, Cultured; Consortia; Gene Function; Genealogy; Genetic aspects; Genetics; Genome-Wide Association Study; Genomes; Genomics; Genotypes; Human Genetics; Humans; Hypertension - genetics; Hypertension - pathology; Hypotheses; Kardiologi; Klinisk medicin; Life Sciences; Medical and Health Sciences; Medical Genetics; Medical schools; Medicin och hälsovetenskap; Medicinsk genetik; Medicinska och farmaceutiska grundvetenskaper; Meta-analysis; Microarray Analysis; Polymorphism, Single Nucleotide; Studies
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.3667

Patricia Munroe, Christopher Newton-Cheh, Andrew Morris and colleagues perform association studies in over 340,000 individuals of European ancestry and identify 66 loci, of which 17 are novel, involved in blood pressure regulation. The risk SNPs are enriched for cis -regulatory elements, particularly in vascular endothelial cells. 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.