Table 1.

Summary of selected main GWAS category based findings and lessons learned

Primary PhenotypeChrGeneSelected Top SNPStudy PopulationCommentsLessons Learned
eGFR (general population)2NAT8rs13538; rs10206899European, TransethnicAlso associated with CKDClose to 100 loci identified with small effect size
Reasonable gene-level consistency across ancestral background
Numerous loci were also associated with CKD, but not ESRD (e.g., SHROOM3,NAT8, DAB2, and WDR37)
Most gene variants identified in general population cohorts have minimal prognostic power, but are able to identify many novel pathways, delineate underlying pathophysiology, and identify potential therapeutic treatments (e.g., UMOD)
4SHROOM3rs13146355; rs17319721; rs5020545Asian, European, TransethnicAlso associated with CKD
5DAB2rs11959928European, TransethnicAlso associated with CKD
6SLC22A2rs2279463; rs316009European, Transethnic
10WDR37rs10794720EuropeanAlso associated with CKD
15WDR72rs17730436; rs491567; rs1031755Asian, European, Transethnic
16UMODrs11864909; rs12917707Asian, EuropeanAlso associated with CKD, ESRD, and hypertension. Would lead to kidney lesions through activation of the NKCC2 transporter, which can be blocked by furosemide (potential translation to clinical care)
Progression rate of CKD15LINC00923rs653747African ancestryAlso associated with ESRD and proteinuria. Similar trend in European Americans. Minimal overlap noted with eGFR-associated SNPsContext-specificity of genotype-phenotype associations (established CKD versus general population)
Albuminuria10CUBNrs1801239EuropeanSimilar trend in blacks. Also associated with ESRD in Europeans and ESRD in diabetic blacks. Also associated with kidney graft failure in EuropeansContext-specificity of genotype-phenotype associations (CKD versus general population versus diabetic population)
Diabetic nephropathy2AFF3rs7583877EuropeanType 1 diabetes–associated ESRDNone of these signals were consistently replicated demonstrating a complex genetic landscape
Possible role for epigenetic mechanisms and/or multiple interactions
2CDCA7-SP3rs4972593EuropeanType 1 diabetes–associated ESRD in women
6SCAF8rs955333TransethnicType 2 diabetic nephropathy
13MYO16-IRS2rs9521445; rs1411766TransethnicBoth type 1 and type 2 diabetic nephropathy
15RGMA-MCTP2rs12437854EuropeanType 1 diabetes–associated ESRD
Membranous nephropathy2PLA2R1rs4664308EuropeanCorrelated with anti-PLA2R1 antibodies in patients with MN
Antibody dosing used for diagnosis, response prediction to immunosuppressive therapy, long-term outcomes prediction (translation to clinical care)Focus on homogeneous disease phenotype even in face of small sample sizes can reveal strong associations
Major epistatic effect involved (OR, 78 CI, 34.6–178.2)
6HLA-DQA1rs2187668EuropeanAlso associated with lupus nephritis, type 1 diabetic nephropathy, and FSGS in adults. Associated with steroid-sensitive nephrotic syndrome
IgA nephropathy1VAV3rs17019602TransethnicNumerous variants identified. High overlap with diverse autoimmune genesComplex, multilocus model may be needed to better capture overall genotypic effect. Importance of pathogen-driven selective pressure to shape beneficial versus pathogenic immune responses
6HLA genesrs2523946; rs1883414; rs1794275; rs660895Asian, Transethnic
8DEFArs2738048; rs10086568Asian, Transethnic
16ITGAMrs7190997; rs11574637Asian, Transethnic
FSGS-HIVAN, Hypertension-attributed ESRD22APOL1rs73885319; rs71785313African ancestryStrong recessive pattern Associated with CKD progression rate from diverse etiologies. Modest association with proteinuria. Associated with faster kidney allograft failure (potential translation to clinical care)Can have common variant with strong effect in face of strong selection factors. Importance of well characterized homogeneous phenotypes (e.g., HIVAN)
Highly variable gene effect on the basis of studied population (e.g., minimal association with eGFR in general population)
  • Chr, chromosome; SNP, single nucleotide polymorphism; OR, odds ratio; HIVAN, HIV-associated nephropathy.