Forskning ved Københavns Universitet - Københavns Universitet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Georg B Ehret
  • Teresa Ferreira
  • Daniel I Chasman
  • Anne U Jackson
  • Ellen M Schmidt
  • Toby Johnson
  • Gudmar Thorleifsson
  • Jian'an Luan
  • Louise A Donnelly
  • Stavroula Kanoni
  • Ann-Kristin Petersen
  • Vasyl Pihur
  • Rona J Strawbridge
  • Dmitry Shungin
  • Maria F 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 Magnusson
  • Elias L Salfati
  • Loukianos S Rallidis
  • Elizabeth Theusch
  • Andrew J P Smith
  • Lasse Folkersen
  • Kate Witkowska
  • Pers, Tune H
  • Roby Joehanes
  • Stuart K Kim
  • Lazaros Lataniotis
  • Rick Jansen
  • Andrew D Johnson
  • Helen Warren
  • Young Jin Kim
  • Wei Zhao
  • Ying Wu
  • Bamidele O Tayo
  • Murielle Bochud
  • Devin Absher
  • Linda S Adair
  • Najaf Amin
  • Inger Njølstad
  • Schwarz, Peter
  • CHARGE-EchoGen Consortium

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.

OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind48
Udgave nummer10
Sider (fra-til)1171-1184
Antal sider14
ISSN1061-4036
DOI
StatusUdgivet - 12 sep. 2016

ID: 165941125