CKDGen Consortium Meta-Analysis Data

Teumer, Li, Ghasemi, Prins, Wuttke, and Hermle et al., 2019

https://pubmed.ncbi.nlm.nih.gov/31511532/

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.

Data set description

• Analyses of UACR and Microalbuminuria; overall and Diabetes-mellitus, amongst individuals of African American and European American ancestry; and trans-ethnic

• Microalbuminuria: n=348,954 (51,861 cases, 297,093 controls)

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

  • Chr: chromosome
  • Pos_b37: position (build 37)
  • RSID: rs identifier
  • Allele1: coded (effect) allele
  • Allele2: noncoded allele
  • Freq1: frequency of allele 1
  • Effect: beta coefficient for allele 1
  • StdErr: Standard error, no 2nd GC correction
  • P-value: P value
  • N_total_sum: Number of subjects in analysis

Phenotypes

• UACR overall, trans-ethnic n(studies) >= 27, sumMac >= 400
• UACR Diabetes mellitus, trans-ethnic n(studies) >= 18, sumMac >= 400
• UACR overall, European-American ancestry n(studies) >= 18, sumMac >= 400
• UACR overall, African-American ancestry n(studies) >= 1, sumMac >= 400
• Microalbuminuria overall, trans-ethnic n(studies) >= 18, sumMac >= 400

Files

• DATA_DESCRIPTION.txt
• MD5SUM
• formatted_20170020-UACR_DM-All-nstud_18-SumMac_400.tbl.rsid.gz
• formatted_20170711-UACR_overall-ALL-nstud_27-sumMac_400.tbl.rsid.gz
• formatted_20180202-UACR_overall-AA-nstud_1-SumMac_400.rsid.tbl.gz
• formatted_20180205-MA_overall-ALL-nstud_18-SumMac_400.tbl.rsid.gz
• formatted_20180517-UACR_overall-EA-nstud_18-SumMac_400.tbl.rsid.gz