A kidney disorder causing heavy protein loss in urine, usually responsive to steroid treatment in children — a 2018 transethnic GWAS across European, African and Maghrebian ancestries found a strong HLA-DRB1 risk association.
Childhood steroid-sensitive nephrotic syndrome is a kidney disorder in which the filtering units of the kidney leak large amounts of protein into the urine, causing swelling and other symptoms. "Steroid-sensitive" means it responds to corticosteroid treatment, which distinguishes it from the steroid-resistant form with a different clinical course.
This 2018 study did something its own title states directly: a transethnic analysis, combining 244 European-ancestry, 56 African-ancestry and 85 Maghrebian-ancestry cases against matched controls from each group (2,552, 454 and 261 controls respectively). rs28366266, in the HLA-DRB1 region, reached genome-wide significance in the combined transethnic analysis (p=4×10⁻²⁰): each copy of the risk allele (C) was associated with roughly 3.03 times the odds of the condition (95% CI 2.40–3.85) — a notably strong effect for a common variant.
HLA-DRB1 is part of the immune system's antigen-presentation machinery, consistent with the paper's own framing of "immune-related risk alleles" in its title. A separate, European-only sub-analysis of the same study found a weaker association at the same position (odds ratio 2.25) — this page cites the larger, transethnic figures as primary, since they match the study's stated design and combine more statistical power.
Positions joined since this page was written
What this is The text above discusses the variants this page was written around. Since then the catalogue has joined 9 more positions to it, by shared trait or shared paper. They are listed here by the paper each came from; the text does not describe them, and each variant page carries that study's own record.
Barry A et al. 2023, Nature communications rs2637678 (near CALHM6), rs412175 (NPHS1), rs2857607 (NFKBIL1), rs8062322 (CLEC16A), rs2856696 (near HLA-DQB1), rs1794497 (near HLA-DQB1), rs9271747 (near HLA-DQA1), rs9274740 (near HLA-DQB1) — PMID:37120605
Jia X et al. 2020, Kidney international rs2285450 (NPHS1) — PMID:32554042
2026-08-01 · Novel immune-related susceptibility loci associated with pediatric steroid-sensitive nephrotic syndrome identified by a transethnic genome-wide association study. Nephrology Dialysis Transplantation. 2026. DOI:10.1093/ndt/gfag041
This site's childhood steroid-sensitive nephrotic syndrome (SSNS) page currently carries just one variant, in HLA-DRB1. This study, combining a Chinese-ancestry discovery GWAS (510 cases, 1,062 controls) with a transethnic meta-analysis (2,942 cases, 37,041 controls total), found two new genome-wide significant loci, both immune-related: rs4309200 near M6PR-KLRG1 (P=4.70x10^-9, OR=1.23, increasing risk) and rs9303279 near GSDMB-ORMDL3 (P=7.25x10^-9, OR=0.82, protective). Colocalization and Mendelian randomization traced the mechanism to specific immune cell types: genetically higher M6PR expression in NK cells and effector-memory CD4+ T cells increased SSNS risk, while higher ORMDL3 expression in memory B cells and the same CD4+ T cell subset lowered it -- a cell-type-specific immune mechanism rather than a generic inflammatory signal. Separately, a polygenic risk score built from these findings was associated with earlier age of disease onset, an association the study found was largely driven by a specific NPHS1 variant, rs56117924 -- NPHS1 being the same gene family already represented on this site's page (the existing HLA-DRB1 variant, rs28366266, is a different locus). This adds two new, well-powered variants to a page that previously had only one.
Childhood steroid-sensitive nephrotic syndrome is diagnosed by urine protein testing and clinical response to corticosteroid treatment — not by genotype. rs28366266 is not used by any guideline to diagnose the condition or decide treatment in an individual.
Treatment is corticosteroids, to which most children with this form respond — the "steroid-sensitive" label is itself a clinical observation, not a genetic classification. The variant on this page describes population-level genetic risk from a research study; it does not change how an individual child is diagnosed or treated.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Childhood Steroid-Sensitive Nephrotic Syndrome comes down to these specific, well-studied positions — not a diagnosis.
near CALHM6 · rs2637678
See detailed info →near HLA-DQB1 · rs2856696
See detailed info →near HLA-DQB1 · rs1794497
See detailed info →near HLA-DQA1 · rs9271747
See detailed info →near HLA-DQB1 · rs9274740
See detailed info →The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 1 of 10 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
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Childhood Steroid-Sensitive Nephrotic Syndrome. MyGeneLog™. https://www.mygenelog.com/conditions/childhood-steroid-sensitive-nephrotic-syndrome
It is a kidney disorder in which the filtering units of the kidney leak large amounts of protein into the urine. "Steroid-sensitive" means it responds to corticosteroid treatment.
Combining 244 European-ancestry, 56 African-ancestry and 85 Maghrebian-ancestry cases against matched controls, it found a genome-wide significant variant in the HLA-DRB1 region, with each risk allele copy linked to roughly 3.03 times the odds of the condition.
By common-variant standards, yes -- an odds ratio around 3 is notably strong, consistent with the immune system's established role in this condition.
No. Diagnosis is by urine protein testing and clinical response to corticosteroid treatment -- not genotype.
Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog™. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.