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Eleven genomic loci affect plasma levels of chronic inflammation marker soluble urokinase-type plasminogen activator receptor.

Publication ,  Journal Article
Dowsett, J; Ferkingstad, E; Rasmussen, LJH; Thørner, LW; Magnússon, MK; Sugden, K; Thorleifsson, G; Frigge, M; Burgdorf, KS; Ostrowski, SR ...
Published in: Communications biology
June 2021

Soluble urokinase-type plasminogen activator receptor (suPAR) is a chronic inflammation marker associated with the development of a range of diseases, including cancer and cardiovascular disease. The genetics of suPAR remain unexplored but may shed light on the biology of the marker and its connection to outcomes. We report a heritability estimate of 60% for the variation in suPAR and performed a genome-wide association meta-analysis on suPAR levels measured in Iceland (N = 35,559) and in Denmark (N = 12,177). We identified 13 independently genome-wide significant sequence variants associated with suPAR across 11 distinct loci. Associated variants were found in and around genes encoding uPAR (PLAUR), its ligand uPA (PLAU), the kidney-disease-associated gene PLA2R1 as well as genes with relations to glycosylation, glycoprotein biosynthesis, and the immune response. These findings provide new insight into the causes of variation in suPAR plasma levels, which may clarify suPAR's potential role in associated diseases, as well as the underlying mechanisms that give suPAR its prognostic value as a unique marker of chronic inflammation.

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Published In

Communications biology

DOI

EISSN

2399-3642

ISSN

2399-3642

Publication Date

June 2021

Volume

4

Issue

1

Start / End Page

655

Related Subject Headings

  • Receptors, Urokinase Plasminogen Activator
  • Quantitative Trait, Heritable
  • Polymorphism, Single Nucleotide
  • Multifactorial Inheritance
  • Male
  • Inflammation Mediators
  • Humans
  • Genome-Wide Association Study
  • Female
  • Cohort Studies
 

Citation

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Dowsett, J., Ferkingstad, E., Rasmussen, L. J. H., Thørner, L. W., Magnússon, M. K., Sugden, K., … Ullum, H. (2021). Eleven genomic loci affect plasma levels of chronic inflammation marker soluble urokinase-type plasminogen activator receptor. Communications Biology, 4(1), 655. https://doi.org/10.1038/s42003-021-02144-8
Dowsett, Joseph, Egil Ferkingstad, Line Jee Hartmann Rasmussen, Lise Wegner Thørner, Magnús K. Magnússon, Karen Sugden, Gudmar Thorleifsson, et al. “Eleven genomic loci affect plasma levels of chronic inflammation marker soluble urokinase-type plasminogen activator receptor.Communications Biology 4, no. 1 (June 2021): 655. https://doi.org/10.1038/s42003-021-02144-8.
Dowsett J, Ferkingstad E, Rasmussen LJH, Thørner LW, Magnússon MK, Sugden K, et al. Eleven genomic loci affect plasma levels of chronic inflammation marker soluble urokinase-type plasminogen activator receptor. Communications biology. 2021 Jun;4(1):655.
Dowsett, Joseph, et al. “Eleven genomic loci affect plasma levels of chronic inflammation marker soluble urokinase-type plasminogen activator receptor.Communications Biology, vol. 4, no. 1, June 2021, p. 655. Epmc, doi:10.1038/s42003-021-02144-8.
Dowsett J, Ferkingstad E, Rasmussen LJH, Thørner LW, Magnússon MK, Sugden K, Thorleifsson G, Frigge M, Burgdorf KS, Ostrowski SR, Sørensen E, Erikstrup C, Pedersen OB, Hansen TF, Banasik K, Brunak S, DBDS Genomic Consortium, Tragante V, Lund SH, Stefansdottir L, Gunnarson B, Poulton R, Arseneault L, Caspi A, Moffitt TE, Gudbjartsson D, Eugen-Olsen J, Stefánsson H, Stefánsson K, Ullum H. Eleven genomic loci affect plasma levels of chronic inflammation marker soluble urokinase-type plasminogen activator receptor. Communications biology. 2021 Jun;4(1):655.

Published In

Communications biology

DOI

EISSN

2399-3642

ISSN

2399-3642

Publication Date

June 2021

Volume

4

Issue

1

Start / End Page

655

Related Subject Headings

  • Receptors, Urokinase Plasminogen Activator
  • Quantitative Trait, Heritable
  • Polymorphism, Single Nucleotide
  • Multifactorial Inheritance
  • Male
  • Inflammation Mediators
  • Humans
  • Genome-Wide Association Study
  • Female
  • Cohort Studies