CKDGen Consortium Meta-Analysis Data

Pattaro, Teumer, Gorski, Chu, Li, and Mijatovic et al., 2016

https://pubmed.ncbi.nlm.nih.gov/26831199/

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

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.

Data set description

• Analyses are performed among participants of European ancestry unless otherwise specified

• DM and nonDM indicate results from analyses stratified by diabetes status

• All other analyses were performed in the overall group

• eGFRcrea_AA were performed among African American participants

• Within each file, the data are presented as follows:

  • rsID: is the rs-identifier
  • allele1: is the coded allele
  • allele2: is the noncoded allele
  • freqA1: is the frequency of allele1 from the Hapmap CEU (European ancestry analyses) or HapMap YRI (African ancestry analyses)
  • beta: is the beta-coefficient for allele1 (rounded to 2 significant digits)
  • se: is the double GC corrected standard error (rounded to 2 significant digits)
  • pval: is the double GC corrected p-value (rounded to 2 significant digits)
  • N: is the sample size

Phenotypes

• eGFRcrea, Nmax=133,814
• eGFRcrea_DM, Nmax=11,529(Updated 3/16/2016)
• eGFRcrea_nonDM, Nmax=118,460
• eGFRcys, Nmax=33,152
• CKD, Nmax=118,147
• eGFRcrea_AA, Nmax=16,474

Citation

Reference The preferred citation is as follows:

• Pattaro C, Teumer A, Gorski M, et al. Genetic Associations at 53 Loci Highlight Cell Types and Biologic Pathways for Kidney Function. Nat Commun. 2016 Jan 21;7:10023

Files

• formatted_AA_eGFRcrea_overall_2GC_b36_MAFget005_Nget50.csv.gz
• formatted_round3meta_CKD_overall_IV_2GC_b36_MAFget005_Nget50_20120725_b37.csv.gz
• formatted_round3meta_eGFRcrea_DM_IV_2GC_b36_MAFget005_Nget50_20140331.csv.gz
• formatted_round3meta_eGFRcrea_nonDM_IV_2GC_b36_MAFget005_Nget50_20120627_b37.csv.gz
• formatted_round3meta_eGFRcrea_overall_IV_2GC_b36_MAFget005_Nget50_20120705_b37.csv.gz
• formatted_round3meta_eGFRcys_overall_IV_2GC_b36_MAFget005_Nget50_20120725_b37.csv.gz