TY - JOUR
T1 - Eleven genomic loci affect plasma levels of chronic inflammation marker soluble urokinase-type plasminogen activator receptor
AU - Dowsett, Joseph
AU - Ferkingstad, Egil
AU - Rasmussen, Line Jee Hartmann
AU - Thørner, Lise Wegner
AU - Magnússon, Magnús K
AU - Sugden, Karen
AU - Thorleifsson, Gudmar
AU - Frigge, Mike
AU - Burgdorf, Kristoffer Sølvsten
AU - Ostrowski, Sisse Rye
AU - Sørensen, Erik
AU - Erikstrup, Christian
AU - Pedersen, Ole Birger
AU - Hansen, Thomas Folkmann
AU - Banasik, Karina
AU - Brunak, Søren
AU - DBDS Genomic Consortium
AU - Tragante, Vinicius
AU - Lund, Sigrun Helga
AU - Stefansdottir, Lilja
AU - Gunnarson, Bjarni
AU - Poulton, Richie
AU - Arseneault, Louise
AU - Caspi, Avshalom
AU - Moffitt, Terrie E
AU - Gudbjartsson, Daníel
AU - Eugen-Olsen, Jesper
AU - Stefánsson, Hreinn
AU - Stefánsson, Kári
AU - Ullum, Henrik
A2 - Nyegaard, Mette
PY - 2021/6/2
Y1 - 2021/6/2
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Biomarkers/blood
KW - C-Reactive Protein/genetics
KW - Chromosome Mapping
KW - Cohort Studies
KW - Female
KW - Genome-Wide Association Study
KW - Humans
KW - Inflammation Mediators/blood
KW - Male
KW - Multifactorial Inheritance
KW - Polymorphism, Single Nucleotide
KW - Quantitative Trait, Heritable
KW - Receptors, Urokinase Plasminogen Activator/blood
UR - http://www.scopus.com/inward/record.url?scp=85113872153&partnerID=8YFLogxK
U2 - 10.1038/s42003-021-02144-8
DO - 10.1038/s42003-021-02144-8
M3 - Journal article
C2 - 34079037
SN - 2399-3642
VL - 4
SP - 655
JO - Communications Biology
JF - Communications Biology
IS - 1
ER -