Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

et al., Praveen Surendran, Cristiano Fava, Olle Melander, Marju Orho-Melander, Alaitz Poveda, Tibor V. Varga, Frida Renström, Paul Franks, Tiinamaija Tuomi, Peter Almgren, Leif Groop, Joanna M. M. Howson

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

21 Citeringar (SciVal)

Sammanfattning

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
Originalspråkengelska
Sidor (från-till)1314-1332
Antal sidor19
TidskriftNature Genetics
Volym52
Utgåva12
DOI
StatusPublished - 2020

Bibliografisk information

Export Date: 9 December 2020

Ämnesklassifikation (UKÄ)

  • Medicinsk genetik
  • Kardiologi

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