Gorski et al., 2015
https://pubmed.ncbi.nlm.nih.gov/25493955/
Genome-wide association study of kidney function decline in individuals of European descent
Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFR decline of 3 ml/min per 1.73 m(2) or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11, and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 h after gentamicin treatment compared with controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline.
Data set description
- Analyses are performed among participants of European ancestry
- CKD and nonCKD indicate results from analyses stratified by CKD status, where CKD is defined as eGFRcrea <60 ml/min per 1.73 m2 at baseline
- All other analyses were performed in the overall group
- Within each file, the data are presented as follows:
- rsID: rs-identifier
- allele1: coded allele
- allele2: noncoded allele
- freqA1: is the frequency of allele1 from the HapMap CEU r28 reference (available at ftp://ftp.ncbi.nlm.nih.gov/hapmap/frequencies/2010-08_phaseII+III/)
- beta: effect is given with 4 digits after the dot
- se: 2nd GC corrected standard error is given with 4 digits after the dot
- pval: double GC corrected p-value rounded to 3 significant digits
- N: Number of subjects in analysis
Phenotypes
- CKDi overall, Nmax=39,248
- CKDi25 overall, Nmax=37,486
- eGFRdecline CKD, Nmax=3,338
- eGFRdecline noCKD, Nmax=39,653
- eGFRdecline overall, Nmax=43,008
- Rapid3 noCKD, Nmax=39,213
- Rapid3 overall, Nmax=42,551
Citation
Reference The preferred citation is as follows:
- Gorski M, Tin A, Garnaas M, et al., Genome-wide association study of kidney function decline in individuals of European descent, Kidney Int, 87 (2015), 1017-29.
Files
- CKDGen_Progression_DiscoveryMeta_CKDi25_overall.csv.gz
- CKDGen_Progression_DiscoveryMeta_CKDi_overall.csv.gz
- CKDGen_Progression_DiscoveryMeta_Rapid3_noCKD.csv.gz
- CKDGen_Progression_DiscoveryMeta_Rapid3_overall.csv.gz
- CKDGen_Progression_DiscoveryMeta_eGFRdecline_CKD.csv.gz
- CKDGen_Progression_DiscoveryMeta_eGFRdecline_noCKD.csv.gz
- CKDGen_Progression_DiscoveryMeta_eGFRdecline_overall.csv.gz