Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

Praveen Surendran, Fotios Drenos, Robin Young, Helen Warren, James P Cook, Alisa K Manning, Niels Grarup, Xueling Sim, Daniel R Barnes, Kate Witkowska, James R Staley, Vinicius Tragante, Taru Tukiainen, Hanieh Yaghootkar, Nicholas Masca, Daniel F Freitag, Teresa Ferreira, Olga Giannakopoulou, Andrew Tinker, Magdalena HarakalovaEvelin Mihailov, Chunyu Liu, Aldi T Kraja, Sune Fallgaard Nielsen, Asif Rasheed, Maria Samuel, Wei Zhao, Lori L Bonnycastle, Anne U Jackson, Narisu Narisu, Amy J Swift, Lorraine Southam, Jonathan Marten, Jeroen R Huyghe, Alena Stančáková, Cristiano Fava, Therese Ohlsson, Angela Matchan, Kathleen E Stirrups, Jette Bork-Jensen, Anette P Gjesing, Jukka Kontto, Markus Perola, Susan Shaw-Hawkins, Aki S Havulinna, He Zhang, Louise A Donnelly, Christopher J Groves, N William Rayner, Frank Kee, CHARGE-Heart Failure Consortium

Research output: Contribution to journalArticlepeer-review

139 Citations (Scopus)

Abstract

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.

Original languageEnglish
Pages (from-to)1151-61
Number of pages11
JournalNature Genetics
Volume48
Issue number10
Early online date12 Sep 2016
DOIs
Publication statusPublished - Oct 2016

Keywords

  • Journal Article

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