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 - Magnusson, Magnus 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 - Folkmann Hansen, Thomas
AU - Banasik, Karina
AU - Brunak, Søren
AU - Andersen, Steffen
AU - Jemec, Gregor Borut Ernst
AU - Jennum, Poul
AU - Nielsen, Kasper René
AU - Nyegaard, Mette
AU - Paarup, Helene Martina
AU - Petersen, Mikkel
AU - Werge, Thomas
AU - Thorsteinsdottir, Unnur
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, Daniel F.
AU - Eugen-Olsen, Jesper
AU - Stefansson, Hreinn
AU - Stefansson, Kari
AU - Ullum, Henrik
AU - DBDS Genomic Consortium
PY - 2021/12
Y1 - 2021/12
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 - Genetic markers
KW - Genome-wide association studies
KW - Inflammatory diseases
KW - Prognostic markers
KW - Quantitative trait
KW - Genetic markers
KW - Genome-wide association studies
KW - Inflammatory diseases
KW - Prognostic markers
KW - Quantitative trait
U2 - 10.1038/s42003-021-02144-8
DO - 10.1038/s42003-021-02144-8
M3 - Journal article
SN - 2399-3642
VL - 4
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 655
ER -
