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Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome
- Source :
- Kidney International, Kidney International, Nature Publishing Group, 2020, ⟨10.1016/j.kint.2020.05.029⟩, Kidney Int
- Publication Year :
- 2020
- Publisher :
- HAL CCSD, 2020.
-
Abstract
- To understand the genetics of steroid-sensitive nephrotic syndrome (SSNS), we conducted a genome-wide association study in 987 childhood SSNS patients and 3,206 healthy controls with Japanese ancestry. Beyond known associations in the HLA-DR/DQ region, common variants in NPHS1-KIRREL2 (rs56117924, P=4.94E-20, odds ratio (OR) =1.90) and TNFSF15 (rs6478109, P=2.54E-8, OR=0.72) regions achieved genome-wide significance and were replicated in Korean, South Asian and African populations. Trans-ethnic meta-analyses including Japanese, Korean, South Asian, African, European, Hispanic and Maghrebian populations confirmed the significant associations of variants in NPHS1-KIRREL2 (P(meta)=6.71E-28, OR=1.88) and TNFSF15 (P(meta)=5.40E-11, OR=1.33) loci. Analysis of the NPHS1 risk alleles with glomerular NPHS1 mRNA expression from the same person revealed allele specific expression with significantly lower expression of the transcript derived from the risk haplotype (Wilcox test p=9.3E-4). Because rare pathogenic variants in NPHS1 cause congenital nephrotic syndrome of the Finnish type (CNSF), the present study provides further evidence that variation along the allele frequency spectrum in the same gene can cause or contribute to both a rare monogenic disease (CNSF) and a more complex, polygenic disease (SSNS).
- Subjects :
- Tumor Necrosis Factor Ligand Superfamily Member 15
0301 basic medicine
podocyte
Steroid-sensitive nephrotic syndrome
030232 urology & nephrology
Polygenic disease
glomerulus
Biology
Monogenic disease
Article
03 medical and health sciences
0302 clinical medicine
pediatric nephrology
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
medicine
Humans
Child
Gene
Allele frequency
Congenital nephrotic syndrome
Alleles
ComputingMilieux_MISCELLANEOUS
Genetics
nephrotic syndrome
Membrane Proteins
Odds ratio
medicine.disease
3. Good health
030104 developmental biology
Haplotypes
Nephrology
Mutation
Steroids
Nephrotic syndrome
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 00852538 and 15231755
- Database :
- OpenAIRE
- Journal :
- Kidney International, Kidney International, Nature Publishing Group, 2020, ⟨10.1016/j.kint.2020.05.029⟩, Kidney Int
- Accession number :
- edsair.doi.dedup.....2e9f498de3de6242760614976f35b3f9