Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

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

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Triglycerides as a shared risk factor between dementia and atherosclerotic cardiovascular disease: a study of 125 727 individuals

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Genome-wide association study of circulating levels of glucagon during an oral glucose tolerance test

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Genome-Wide Association Analysis of Pancreatic Beta Cell Glucose Sensitivity

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. FUT2-ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. The effect of diabetes and the common diabetogenic TBC1D4 p.Arg684Ter variant on cardiovascular risk in Inuit in Greenland

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Praveen Surendran
  • Elena V Feofanova
  • Najim Lahrouchi
  • Ioanna Ntalla
  • Savita Karthikeyan
  • James Cook
  • Lingyan Chen
  • Borbala Mifsud
  • Chen Yao
  • Aldi T Kraja
  • James H Cartwright
  • Jacklyn N Hellwege
  • Ayush Giri
  • Vinicius Tragante
  • Gudmar Thorleifsson
  • Dajiang J Liu
  • Bram P Prins
  • Isobel D Stewart
  • Claudia P Cabrera
  • James M Eales
  • Artur Akbarov
  • Paul L Auer
  • Lawrence F Bielak
  • Joshua C Bis
  • Vickie S Braithwaite
  • Jennifer A Brody
  • E Warwick Daw
  • Helen R Warren
  • Fotios Drenos
  • Sune Fallgaard Nielsen
  • Jessica D Faul
  • Eric B Fauman
  • Cristiano Fava
  • Teresa Ferreira
  • Christopher N Foley
  • Nora Franceschini
  • He Gao
  • Olga Giannakopoulou
  • Franco Giulianini
  • Daniel F Gudbjartsson
  • Xiuqing Guo
  • Sarah E Harris
  • Aki S Havulinna
  • Jette Bork-Jensen
  • Torben Hansen
  • Marit E Jørgensen
  • Allan Linneberg
  • Katrine L Rasmussen
  • Tea Skaaby
  • Børge Grønne Nordestgaard
  • LifeLines Cohort study
View graph of relations

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.

Original languageEnglish
JournalNature Genetics
Volume52
Issue number12
Pages (from-to)1314-1332
Number of pages19
ISSN1061-4036
DOIs
Publication statusPublished - 2020

ID: 61317911