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Table 2. Genome-wide association studies of acquired chronic kidney disease
Diseases Sample size Study population Main findings References
IMN 556 patients and 2388 controls European Two loci, PLA2R1 and HLA-DQA1, strongly associated [36]
with IMN risk
IMN 1112 patients and 1020 controls Chinese The interaction between PLA2R1 and HLA-DQA1 variants [37]
contribute to the presence of anti-PLA2R antibodies
IMN 149 patients and 100 controls Chinese HLA-DRB1*15:01 and HLA-DRB3*02:02 alleles [39]
independently and strongly associate with PLA2R-related
IMN
IgAN 244 patients, 4,980 healthy European HLA locus contained the strongest common susceptibility [53]
individuals, 186 families alleles responsible for genetic predisposition to IgAN in
the European population
IgAN 1,950 patients and 1,920 Chinese and Deletions in CFHR1 and CFHR3 were related to a reduced [49]
controls European risk of IgAN
IgAN 500 patients and 576 controls Chinese CFHR5 is a susceptibility gene for IgAN [51]
IgAN 20612 participants European and East Identified 6 new risk loci: 2 new independent signals at [46]
Asian HLA-DQB1 and DEFA; plus 4 in ITGAM-ITGAX, VAV3,
and CARD9
IgAN 8,313 patients and 19,680 Han Chinese The allelic frequencies of the variants within ST6GAL1, [47]
controls ACCS, and DEFA correlated with geographical variations
in IgAN prevalence
IgAN 1000 IgAN cases and 1000 Chinese Genetic variations and gene expression levels of TNFSF13 [56]
controls were related to the susceptibility and severity of IgAN
among the Han population
DN 5,825 with diabetes and 46,061 European SNPs in HS6ST1 and RAB38/CTSC exerted a genetic [75]
without diabetes effect on albuminuria only in individuals with diabetes
DN 743 patients and 646 controls European Loci 11p15.4, near the CARS gene, and 13q33.3 [76]
encompassing an intergenic region between MYO16 and
IRS2 genes, were susceptible to kidney disease in both
type 1 and 2 diabetes
DN 3,652 patients Finnish rs4972593 on chromosome 2q31.1 was a sex-specific [77]
genetic variant related to ESRD in patients with type 1
diabetes
DN 406 patients and 214 controls Chinese rs2796498 might be associated with DN [79]
IMN: idiopathic membranous nephropathy; IgAN: IgA nephropathy; DN: diabetic nephropathy; SNP: single-nucleotide polymorphism;
ESRD: end-stage renal disease

[46]
Kiryluk et al. performed a follow-up evaluation in 20,612 European and East Asian individuals. They
identified 6 new risk loci: 2 new independent signals at HLA-DQB1 and DEFA; plus 4 in ITGAM-ITGAX
(encoding integrin subunits M and X), VAV3, and CARD9 (encoding caspase recruitment domain family
member 9). Li et al. conducted a GWAS comprising 8,313 patients and 19,680 controls. They reported
[47]
that the allelic frequencies of the variants within ST6GAL1 (encoding ST6 beta-galactoside alpha-2,6-
sialyltransferase 1), ACCS (encoding 1-aminocyclopropane-1-carboxylate synthase homolog), and DEFA
[54]
correlated with geographical variations in IgAN prevalence. Milillo et al. reported that a SPRY2 mutation
inhibited the mitogen-associated protein kinase/extracellular signal-related kinase pathway, which was
[55]
associated with an autosomal dominant form of IgAN. Gale et al. reported that a common variation
in C1GALT1 influenced galactose-deficient IgA1 levels in the population, which was independently
[56]
associated with the risk of progressive IgAN. Finally, Zhong et al. reported that genetic variations and
gene expression levels of TNFSF13 were related to the susceptibility and severity of IgAN among the Han
population [Table 2].

Overall, these studies emphasize complex multilocus model for IgAN. Multiple rare variants participating in
a common network can influence disease susceptibility. Future investigations might explore the development
of combined biomarkers to generate a prognostic model which can usher into potential genomic biomarkers
[58]
and drug targets for personalized therapy .

Apolipoprotein L1-related kidney disease
[59]
The incidence of ESRD varies substantially between African and European individuals .