Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
To access publisher's full text version of this article click on the hyperlink at the bottom of the page ; 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. ; HHSN268201100009C/HL/NHLBI NIH HHS/United States K12 RR023250/RR/NCRR NIH HHS/United States P30 DK072488/DK/NIDDK NIH HHS/United States R01 AG018728/AG/NIA NIH HHS/United States R01 AG033193/AG/NIA NIH HHS/United States R01 DK058845/DK/NIDDK NIH HHS/United States R01 DK066574/DK/NIDDK NIH HHS/United States R01 DK075787/DK/NIDDK NIH HHS/United States R01 DK084350/DK/NIDDK NIH HHS/United States R01 DK089256/DK/NIDDK NIH HHS/United States R01 HL087641/HL/NHLBI NIH HHS/United States R01 HL087660/HL/NHLBI NIH HHS/United States R01 HL088119/HL/NHLBI NIH HHS/United States R01 HL117078/HL/NHLBI NIH HHS/United States R01DK090311/DK/NIDDK NIH HHS/United States R24OD017870/OD/NIH HHS/United States T32 HL007024/HL/NHLBI NIH HHS/United States U01 GM074518/GM/NIGMS NIH HHS/United States U01 HG004399/HG/NHGRI NIH HHS/United States U01 ...
