Wuttke, Li Y., Li M., Sieber, Feitosa, Gorski et al., 2019

https://pubmed.ncbi.nlm.nih.gov/31152163/

A catalog of genetic loci associated with kidney function from analyses of a million individuals

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.

Data set description

Analyses of eGFR, BUN and CKD; amonst individuals of European American ancestry, and trans-ethnic
CKD EA: n=480,698 (41,395 cases and 439,303 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

eGFRcrea overall, trans-ethnic, (n(studies) >= 61)
eGFRcrea overall, European ancestry, (n(studies) >= 42)
BUN overall, trans-ethnic, (n(studies) >= 33)
BUN overall, European ancestry, (n(studies) >= 24)
CKD overall, trans-ethnic, (n(studies) >= 30)
CKD overall, European ancestry, (n(studies) >= 23)