Abstract: TH-PO450
Differences in Peripheral Blood Cell DNA Methylation Between Nephrotic Syndrome Subgroups
Session Information
- Glomerular Diseases: Podocytopathies and Nephrotic Syndromes
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials
Authors
- Hayward, Samantha JL, University of Bristol Translational Health Sciences, Bristol, England, United Kingdom
- Bierzynska, Agnieszka, University of Bristol Translational Health Sciences, Bristol, England, United Kingdom
- Welsh, Gavin Iain, University of Bristol Translational Health Sciences, Bristol, England, United Kingdom
- Suderman, Matthew, MRC Integrative Epidemiology Unit, Bristol, Bristol, United Kingdom
- Saleem, Moin, University of Bristol Translational Health Sciences, Bristol, England, United Kingdom
Group or Team Name
- Bristol Renal
Background
Genetic and observational research suggest that at least 4 mechanistically different subgroups of paediatric nephrotic syndrome (NS) exist: genetic steroid resistant NS (SRNS), non-genetic SRNS, steroid sensitive NS (SSNS) and circulating factor disease (CFD). We explored differences in DNA methylation (DNAm), an epigenetic mechanism, between the 4 different NS subgroups.
Methods
322 patients were selected from the NephroS-NURTuRE NS cohort. All patients were diagnosed with NS ≤30 years of age. Patients were split a priori into the 4 NS subgroups based upon their genetic and clinical data. Peripheral blood cell DNAm values were generated using the Illumina EPIC array (>850,000 CpG sites). Generalised linear models were used to assess differences in DNAm between the NS subgroups at each individual CpG site. Differentially methylated regions (DMRs) were assessed using the dmrff R package. All analyses were adjusted for cell type proportions, age and sex. Sex chromosomes were excluded from the analyses. A Bonferroni adjusted p value of 5.88x10-8 was used as a significance threshold.
Results
Differing DNAm was identified at 7 individual CpG sites and 1 DMR (p values <5.88 x 10-7) between the NS subgroups. Only 1 of these CpG sites reached our significance threshold (Figure 1, p=1.88x10-08); differing DNAm at this site was detected between patients with non-genetic SRNS and genetic SRNS. This CpG is found in the transcriptional start site of a transcribed pseudogene, which has plausible biological links to kidney disease.
Conclusion
We have identified a shortlist of interesting sites of differing DNAm between the 4 NS subgroups. Further work, utilising machine learning approaches, to reveal DNAm-based signatures that discriminate between NS subgroups is underway.