Table 1.
SNPs significantly associated with eGFR or CKD in stage 1 meta analysis in the CKDGen Consortium
| Gene Name | Syndrome | SNP ID | Coded Allele Frequency | Trait | P | Phenotype |
|---|---|---|---|---|---|---|
| ACTN4 | FSGS 1, FSGS1 | rs755690 | 0.44 | eGFR | 0.004 | Nephrotic syndrome, ESRD |
| AGXT | Primary hyperoxaluria type I | rs4538195 | 0.06 | CKD | 0.01 | Calcium oxalate accumulation and renal failure |
| AQP2 | Nephrogenic diabetes insipidus, autosomal | rs296736 | 0.52 | eGFR | 0.004 | Diabetes insipidus |
| BBS1 | Bardet-Biedl syndrome (BBS) | rs1671062 | 0.40 | eGFR | 0.001 | Developmental abnormalities with common renal failure |
| BMP4 | Syndromic microphthalmia 6 (MCOPS6) | rs11623717 | 0.58 | eGFR | 0.001 | Hypoplastic kidneys, renal failure possible |
| CA2 | Autosomal recessive osteopetrosis 3, (OPTB3) | rs3758078 | 0.36 | eGFR, CKD | 0.01, 0.04 | Isozymes of carbonic anhydrase, associated with RTA |
| CACNA1S | Hypokalemic periodic paralysis (HOKPP) | rs3850625 | 0.12 | eGFR | 0.0004 | Renal phosphate wasting, associated with hypokalemia and episodic weakness |
| CASR | Familial hypocalciuric hypercalcemia type I, HHC1 acquired hypocalciuric hypercalcemia | rs7638770 | 0.25 | eGFR, CKD | 0.001, 0.0003 | PTH-independent renal tubular defect in calcium reabsorption, associated with hypercalcemia and hypermagnesemia |
| CFI | Complement factor I deficiency GN with isolated C3 deposits and factor I deficiency | rs6815517 | 0.72 | CKD | 0.01 | Deficiency of the C3 inactivator associated with GN and renal failure |
| ENG | Hereditary hemorrhagic telangiectasia Rendu-Osler-Weber (HHT) | rs11789185 | 0.10 | eGFR | 0.001 | Vascular dysplasia, associated with rare hematuria |
| ERCC8 | Cockayne syndrome type A (CSA) | rs158938 | 0.65 | eGFR | 0.002 | Immune complex-mediated GN |
| FGF23 | Hyperphosphatemic familial tumoral calcinosis (HFTC) | rs720333 | 0.85 | eGFR, CKD | 0.003, 0.003 | Increase renal absorption of phosphate, associated with deposition of basic calcium phosphate crystals |
| G6PC | Glycogen storage disease I | rs2593595 | 0.82 | CKD | 0.01 | Glycogen storage with renal failure |
| GIF | Intrinsic factor deficiency (IFD) | rs558660 | 0.18 | eGFR | 0.01 | Cobalamin transport, associated with tubular proteinuria |
| GSS | Glutathione synthetase deficiency | rs2236270 | 0.39 | eGFR | 0.0002 | Urinary excretion of 5-oxoproline, associated with metabolic acidosis, RTA |
| HOXD13 | VACTERL association | rs847148 | 0.69 | eGFR | 0.001 | Dysplasia, hydronephrosis with likely failure |
| ICK | Endocrine-cerebroosteodysplasia (ECO) | rs316144 | 0.43 | eGFR | 0.001 | Cystically dilated renal tubules |
| INF2 | FSGS 5 (FSGS5) | rs7140154 | 0.18 | eGFR | 0.01 | FSGS, may lead to ESRD |
| JAG1 | Alagille syndrome 1 (ALGS1) | rs6040050 | 0.29 | eGFR | 0.0004 | Renal dysplasia, renal mesangiolipidosis, medullary cystic disease |
| KCNJ1 | Bartter syndrome, antenatal type 2 | rs2238009 | 0.14 | eGFR | 0.01 | Potassium channel, associated with salt wasting, hypokalemic alkalosis, hypercalciuria, low BP, and nephrocalcinosis Potassium channel, associated with salt wasting, hypokalemic alkalosis, hypercalciuria, low BP, and nephrocalcinosis |
| KRAS | Cardiofaciocutaneous syndrome | rs7960917 | 0.78 | eGFR | 0.001 | Prenatal hydronephrosis, reflux |
| LAMB2 | Pierson syndrome | rs9880088 | 0.10 | eGFR, CKD | 0.0002, 0.02 | Congenital nephrotic syndrome; early onset ESRD |
| LCAT | Lecithin: cholesterol acyltransferase deficiency (LCAT) | rs2292318 | 0.13 | eGFR, CKD | 0.01, 0.01 | Proteinuria and renal failure |
| LRP2 | Donnai-Barrow syndrome | rs6433115 | 0.79 | eGFR | 3.5×10−6 | Proteinuria |
| MKKS | McKusick-Kaufman syndrome (MKKS) | rs6032878 | 0.89 | eGFR | 0.01 | Reproductive system developmental abnormalities, with possible renal failure |
| MMACHC | Methylmalonic aciduria and homocystinuria, type cblC | rs12029322 | 0.22 | eGFR | 0.004 | Thrombotic microangiopathic nephropathy, hematuria, proteinuria, and renal failure |
| NEU1 | Neuramidase deficiency sialidosis type I | rs13118 | 0.93 | eGFR | 0.003 | Lysosomal storage, sialyloligosacchariduria |
| NSD1 | Sotos syndrome | rs4073745 | 0.69 | eGFR, CKD | 3.7×10−6, 0.002 | Rare vesicoureteric reflux |
| PALB2 | Fanconi anemia | rs249942 | 0.10 | eGFR, CKD | 0.002, 0.0002 | CAKUT, renal malformations |
| PKD2 | Autosomal dominant polycystic kidney disease (ADPKD) | rs2728111 | 0.77 | eGFR, CKD | 0.01, 0.01 | Renal cysts, ESRD |
| PLCE1 | Early onset nephrotic syndrome (NPHS3) | rs12258052 | 0.31 | eGFR | 0.001 | FSGS, nephrotic proteinuria, and ESRD |
| PROKR2 | Kallmann syndrome 3 (KAL3) | rs6053283 | 0.25 | eGFR | 0.01 | Reproductive dysfunction, angiogenesis, renal agenesis |
| PSTPIP1 | Pyogenic sterile arthritis, pyoderma gangrenosum, and acne | rs3936040 | 0.17 | eGFR | 0.01 | Proteinuria, possibly immune mediated |
| PVRL1 | Cleft palate ectodermal dysplasia syndrome (CLPED1); orofacial cleft 7 (OFC7) | rs7122134 | 0.60 | eGFR | 0.01 | Renal dysplasia |
| RECQL4 | Baller-Gerold syndrome (BGS) | rs10111332 | 0.52 | eGFR | 0.003 | Renal dysplasia |
| RET | Ret protooncogene | rs1864405 | 0.25 | eGFR | 0.002 | Renal agenesis, vesicoureteric reflux |
| ROBO2 | Vesicoureteral reflux 2 (VUR2) | rs9827843 | 0.58 | eGFR | 0.001 | CAKUT, reflux nephropathy |
| SCARB2 | Action myoclonus-renal failure syndrome (AMRF) | rs894250 | 0.50 | eGFR | 0.001 | FSGS, nephrotic syndrome, renal failure |
| SCNN1B | Liddle syndrome | rs2106374 | 0.81 | eGFR | 0.001 | Hypertension, renal failure rare |
| SLC7A9 | Cystinuria type A | rs12460876 | 0.61 | eGFR, CKD | 9.5×10−12, 0.004 | Cystine precipitation, obstruction, and renal failure |
| SOX17 | Vesicoureteral reflux 1 (VUR1) | rs16920355 | 0.16 | CKD | 0.004 | CAKUT and ESRD |
| STRA6 | Syndromic microphthalmia 9 (MCOPS9) | rs974456 | 0.23 | eGFR | 0.002 | Horseshoe kidney, hydronephrosis, hypoplasia, can lead to ESRD |
| SUCLA2 | Autosomal recessive mitochondrial DNA depletion syndrome, encephalopathic form with methylmalonic aciduria | rs6561429 | 0.91 | CKD | 0.003 | Possibly mitochondrial DNA depletion, rare renal tubular dysfunction |
| TBX1 | Di George syndrome (DGS) | rs4819843 | 0.19 | CKD | 0.01 | Renal hypoplasia, renal insufficiency |
| TSC1 | Tuberous sclerosis 1 (TSC1) | rs1050700 | 0.71 | eGFR | 0.00004 | Renal cysts and tumors, without kidney failure |
| TTC8 | Bardet-Biedl syndrome (BBS) | rs17700521 | 0.73 | eGFR, CKD | 0.001, 0.01 | Developmental abnormalities with common renal failure |
| UMOD | Medullary cystic kidney disease 2 (MCKD2) | rs12922822 | 0.18 | eGFR, CKD | 1.2×10−25, 5.5×10−17 | Medullary cysts with gouty arthritis |
| USF2 | Upstream stimulatory factor 2 | rs1882694 | 0.65 | eGFR | 0.002 | Cystic renal dysplasia and hypodysplasia |
| WDPCP | Bardet-Biedl syndrome (BBS 1–15) | rs1850983 | 0.97 | eGFR, CKD | 0.001, 0.002 | Developmental abnormalities with common renal failure |
Results are from meta-analysis of 74,354 participants. Gene-specific significance thresholds were defined according to the Bonferroni method, as 0.05/ number of independent LD blocks within each gene. If a locus was significantly associated with both eGFR (<60 ml/min per 1.73 m2) and CKD, both P values are provided, respectively. RTA, renal tubular acidosis; PTH, parathyroid hormone; CAKUT, congenital anomalies of the kidney and urinary tract.