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Abstract:
Reduced glomerular filtration rate defines chronic kidney disease and is
associated with cardiovascular and all-cause mortality. We conducted a
meta-analysis of genome-wide association studies for estimated
glomerular filtration rate (eGFR), combining data across 133,413
individuals with replication in up to 42,166 individuals. We identify 24
new and confirm 29 previously identified loci. Of these 53 loci, 19
associate with eGFR among individuals with diabetes. Using
bioinformatics, we show that identified genes at eGFR loci are enriched
for expression in kidney tissues and in pathways relevant for kidney
development and transmembrane transporter activity, kidney structure,
and regulation of glucose metabolism. Chromatin state mapping and DNase
I hypersensitivity analyses across adult tissues demonstrate
preferential mapping of associated variants to regulatory regions in
kidney but not extra-renal tissues. These findings suggest that genetic
determinants of eGFR are mediated largely through direct effects within
the kidney and highlight important cell types and biological pathways.
