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Paul Franks

Paul Franks

Principal investigator

Paul Franks

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

Author

  • 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

Summary, in English

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.

Department/s

  • Cardiovascular Research - Hypertension
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health
  • Diabetes - Cardiovascular Disease
  • Genetic and Molecular Epidemiology
  • Diabetic Complications
  • Genomics, Diabetes and Endocrinology

Publishing year

2020

Language

English

Pages

1314-1332

Publication/Series

Nature Genetics

Volume

52

Issue

12

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Medical Genetics
  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Cardiovascular Research - Hypertension
  • Diabetes - Cardiovascular Disease
  • Genetic and Molecular Epidemiology
  • Diabetic Complications
  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1546-1718