Table 2.
Highlighted genes with novel evidence for kidney function.
| Gene | Variant (EAF, PPA), consequence (CADD PHRED) | Novelty |
|---|---|---|
| Single sets | ||
| Known single | ||
| HOXD11 | rs863678 (0.64, 99.9%), 3’ UTR (18.4) | Not further described previously as “other CADD>=15” previously |
| Newly single | ||
| CERS2 |
rs267738 (0.46, 99.1%), p.Glu115Ala (32.0) |
Previous cred set size=5 (previous PPA = 46%)7; rs267738 reported in previous GWAS7 and for rate of albuminuria67 |
| PKHD1 |
rs76572975 (0.024, 99.7%), p.Arg3842Leu (23.8) |
Not fine-mapped previously7; rs76572975 as less-frequent variant in rare Mendelian disorder gene |
| SPEG | rs112068790 (0.97, 99.2%), intron (18.3); rs55760516 (0.67, 39.8%), p.Gly2790Arg (22.3) | 1st signal newly single, 2nd signal newly small (cred set size = 2), previously one signal with cred set >57; experimental link to kidney function unknown |
| Novel locus | ||
| GAB1 | rs139323761 (0.027, 99.9%), Intron (21.9) | Experimental link to kidney function unknown |
| PDE7A | rs11557049 (0.065, 99.9%), p.Gly76Glu (24.0) | Experimental link to kidney function unknown |
| RBM47 | rs35529250 (0.006, 99.8%), p.Gly538Arg (28.5) | Experimental link to kidney function unknown |
| Sets 2–5 | ||
| Newly small | ||
| BCAS3 | rs9905761 (0.81*, 36.9%), Intron (15.2) | Experimental link to kidney function unknown |
| CDC14A | rs17420882 (0.72,93.2%), Intron (16.2) | Experimental link to kidney function unknown |
| GALNTL5 | rs6464165 (0.71,49.9%), eQTL tubulo-interstitial; rs10224210 (0.71, 49.9%), eQTL tubulo-interstitial | Previous coloc tubulo-interstitial (PPH4 = 98%)7, coloc confirmed (PPH4 = 98.7%), experimental link to kidney function unknown |
| PPDPF | rs72629024 (0.85, 85.1%), eQTL tubulo-interstitial/glomerular | New coloc tubulo-interstitial/ glomerular (PPH4 = 99.5% / 99.8%); experimental link to kidney function unknown |
| RRAGD | rs854922 (0.092, 90.5%), 5’ UTR (18.0) | Experimental link to kidney function unknown. |
| SLC6A13 | rs10774020 (0.34,51.9%), eQTL tubulo-interstitial; rs11062102 (0.34, 47.5%), eQTL tubulo-interstitial | New coloc tubulo-interstitial (PPH4 = 99.5%), cell-type specific expression in proximal tubulus in both datasets; link to kidney function unclear |
| TFDP2 | rs143710547 (0.08, 58.7%), eQTL tubulo-interstitial | No coloc; experimental link to kidney function unknown |
| TPPP | rs434215 (0.28, 93.2%), eQTL tubulo-interstitial | New coloc tubulo-interstitial (PPH4 = 99.6%); experimental link to kidney function unknown |
| YY1AP1 | rs4971092 (0.88, 83.1%), eQTL tubulo-interstitial | New coloc tubulo-interstitial (PPH4 = 99.3%); link to rare Mendelian disease with potential kidney involvement |
| ZC3HC1 | rs11556924 (0.38, 84.1%), p.Arg363His (27.5) | Experimental link to kidney function unknown |
| Novel locus | ||
| AMPD1 | rs17602729 (0.13, 96.0%), p.Gln45Ter (36.0) | Experimental link to kidney function unknown |
| CPXM1 | rs6084180 (0.80, 82.4%), eQTL glomerulus | Experimental link to kidney function unknown |
| HNF1A |
rs1800574 (0.03, 48.4%) p.Ala98Val (22.7) |
Two variants with identical PPA; less-frequent variant in Mendelian disorder gene with kidney phenotype, previously associated with urate35 |
| IKZF2 |
rs112905092 (0.017, 81.2%) Intron (18.8) |
Experimental link to kidney function unknown |
| NPHS1 |
rs3814995 (0.31, 91.5%) p.Glu117Lys, (25.0) |
rs3814995 as common variant in rare Mendelian kidney disorder gene not reported before |
| SIGIRR | rs117739035 (0.037, 65.9%), p.Ser80Tyr (23.5) | Experimental link to kidney function unknown |
Here we present details on the 23 genes (among the 32 identified by the GPS approach on eGFRcys/BUN-validated, small set relevant variants, Fig. 4) that showed adequate fine-mapping resolution for the respective protein-relevant or kidney-tissue regulatory-relevant variant (PPA > = 10%) and novel evidence compared to the previous work7. A detailed description of the genes can be found in Supplementary Note 3.