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

Ehret, Georg B.; Ferreira, Teresa; Chasman, Daniel I.; Jackson, Anne U.; Schmidt, Ellen M.; Johnson, Toby; Thorleifsson, Gudmar; Luan, Jian'An; Donnelly, Louise A. and Kanoni, Stavroula, et al. (2016) In Nature Genetics 48(10). p.1171-1184
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.... (More)

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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Nature Genetics
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48
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10
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  • scopus:84987625495
  • wos:000384391600012
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1061-4036
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10.1038/ng.3667
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English
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2016-10-28 11:42:29
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2017-11-19 04:34:18
@article{9b0414b3-9f70-45d7-b5ac-80634646e6e5,
  abstract     = {<p>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.</p>},
  author       = {Ehret, Georg B. and Ferreira, Teresa and Chasman, Daniel I. and Jackson, Anne U. and Schmidt, Ellen M. and Johnson, Toby and Thorleifsson, Gudmar and Luan, Jian'An and Donnelly, Louise A. and Kanoni, Stavroula and Petersen, Ann Kristin and Pihur, Vasyl and Strawbridge, Rona J. and Shungin, Dmitry and Hughes, Maria F. and Meirelles, Osorio and Kaakinen, Marika and Bouatia-Naji, Nabila and Kristiansson, Kati and Shah, Sonia and Kleber, Marcus E. and Guo, Xiuqing and Lyytikäinen, Leo Pekka and Fava, Cristiano and Eriksson, Niclas and Nolte, Ilja M. and Magnusson, Patrik K. and Salfati, Elias L. and Rallidis, Loukianos S. and Theusch, Elizabeth and Smith, Andrew J P and Folkersen, Lasse and Witkowska, Kate and Pers, Tune H. and Joehanes, Roby and Kim, Stuart K. and Lataniotis, Lazaros and Jansen, Rick and Johnson, Andrew D. and Warren, Helen and Kim, Young Jin and Zhao, Wei and Wu, Ying and Tayo, Bamidele O. and Bochud, Murielle and Absher, Devin and Adair, Linda S. and Amin, Najaf and Arking, Dan E. and Axelsson, Tomas and Baldassarre, Damiano and Balkau, Beverley and Bandinelli, Stefania and Barnes, Michael R. and Barroso, Inês and Bevan, Stephen and Bis, Joshua C. and Bjornsdottir, Gyda and Boehnke, Michael and Boerwinkle, Eric and Bonnycastle, Lori L. and Boomsma, Dorret I. and Bornstein, Stefan R. and Brown, Morris J. and Burnier, Michel and Cabrera, Claudia P. and Chambers, John C. and Chang, I. Shou and Cheng, Ching Yu and Chines, Peter S. and Chung, Ren Hua and Collins, Francis S. and Connell, John M. and Döring, Angela and Dallongeville, Jean and Danesh, John and De Faire, Ulf and Delgado, Graciela and Dominiczak, Anna F. and Doney, Alex S F and Drenos, Fotios and Edkins, Sarah and Eicher, John D. and Elosua, Roberto and Enroth, Stefan and Erdmann, Jeanette and Eriksson, Per and Esko, Tonu and Evangelou, Evangelos and Evans, Alun and Fall, Tove and Farrall, Martin and Felix, Janine F. and Ferrières, Jean and Ferrucci, Luigi and Fornage, Myriam and Forrester, Terrence and Franceschini, Nora and Franco, Oscar H. and Franco-Cereceda, Anders and Fraser, Ross M. and Ganesh, Santhi K. and Gao, He and Gertow, Karl and Gianfagna, Francesco and Gigante, Bruna and Giulianini, Franco and Goel, Anuj and Goodall, Alison H. and Goodarzi, Mark O. and Gorski, Mathias and Gräßler, Jürgen and Groves, Christopher J. and Gudnason, Vilmundur and Gyllensten, Ulf and Hallmans, Göran and Hartikainen, Anna Liisa and Hassinen, Maija and Havulinna, Aki S. and Hayward, Caroline and Hercberg, Serge and Herzig, Karl Heinz and Hicks, Andrew A. and Hingorani, Aroon D. and Hirschhorn, Joel N. and Hofman, Albert and Holmen, Jostein and Holmen, Oddgeir Lingaas and Hottenga, Jouke Jan and Howard, Phil and Hsiung, Chao A. and Hunt, Steven C. and Ikram, M. 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  issn         = {1061-4036},
  language     = {eng},
  month        = {10},
  number       = {10},
  pages        = {1171--1184},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals},
  url          = {http://dx.doi.org/10.1038/ng.3667},
  volume       = {48},
  year         = {2016},
}