Strong Association of the Locus with Childhood Steroid-Sensitive Nephrotic Syndrome in the Japanese Population.

Nephrotic syndrome is the most common cause of chronic glomerular disease in children. Most of these patients develop steroid-sensitive nephrotic syndrome (SSNS), but the loci conferring susceptibility to childhood SSNS are mainly unknown. We conducted a genome-wide association study (GWAS) in the Japanese population; 224 patients with childhood SSNS and 419 adult healthy controls were genotyped using the Affymetrix Japonica Array in the discovery stage. Imputation for six genes (, , , , and ) was conducted on the basis of Japanese-specific references. We performed genotyping for /- using a sequence-specific oligonucleotide-probing method on a Luminex platform. Whole-genome imputation was conducted using a phased reference panel of 2049 healthy Japanese individuals. Replication was performed in an independent Japanese sample set including 216 patients and 719 healthy controls. We genotyped candidate single-nucleotide polymorphisms using the DigiTag2 assay. The most significant association was detected in the region and replicated (rs4642516 [minor allele G], combined =7.84×10; odds ratio [OR], 0.33; 95% confidence interval [95% CI], 0.26 to 0.41; rs3134996 [minor allele A], combined =1.72×10; OR, 0.29; 95% CI, 0.23 to 0.37). (=1.82×10; OR, 2.62; 95% CI, 1.94 to 3.54) and (=2.09×10; OR, 0.10; 95% CI, 0.05 to 0.21) were considered primary alleles associated with childhood SSNS. (=7.01×10; OR, 3.60; 95% CI, 2.46 to 5.29) was identified as the most significant genetic susceptibility factor. The most significant association with childhood SSNS was detected in the region. Further allele/haplotype analyses should enhance our understanding of molecular mechanisms underlying SSNS.