A catalog of genetic loci associated with kidney function from analyses of a million individuals
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
A catalog of genetic loci associated with kidney function from analyses of a million individuals. / Wuttke, Matthias; Li, Yong; Li, Man; Ahluwalia, Tarunveer S; Christensen, Kaare; LifeLines Cohort Study ; Rossing, Peter; Teumer, Alexander; Köttgen, Anna; Pattaro, Cristian.
I: Nature Genetics, Bind 51, 2019, s. 957-972.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - A catalog of genetic loci associated with kidney function from analyses of a million individuals
AU - Wuttke, Matthias
AU - Li, Yong
AU - Li, Man
AU - Ahluwalia, Tarunveer S
AU - Christensen, Kaare
AU - LifeLines Cohort Study
AU - Rossing, Peter
AU - Teumer, Alexander
AU - Köttgen, Anna
AU - Pattaro, Cristian
PY - 2019
Y1 - 2019
N2 - Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
AB - Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
KW - Chromosome Mapping
KW - European Continental Ancestry Group
KW - Genetic Association Studies/methods
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Glomerular Filtration Rate
KW - Humans
KW - Inheritance Patterns
KW - Kidney Function Tests
KW - Phenotype
KW - Polymorphism, Single Nucleotide
KW - Quantitative Trait Loci
KW - Quantitative Trait, Heritable
KW - Renal Insufficiency, Chronic/genetics
KW - Uromodulin/urine
U2 - 10.1038/s41588-019-0407-x
DO - 10.1038/s41588-019-0407-x
M3 - Journal article
C2 - 31152163
VL - 51
SP - 957
EP - 972
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
ER -
ID: 234084920