Abstract: FR-PO638
Canonical Correlation Analysis Identifies Single Nucleotide Polymorphisms and Gene Expression Associated with CKD Subtypes
Session Information
- Genetic Kidney Diseases: Cohort Studies - Genetic Associations and Diagnoses
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Osborne, Amy J., University of Bristol, Bristol, United Kingdom
- Hayward, Samantha JL, University of Bristol, Bristol, United Kingdom
- Colby, Liz, University of Bristol, Bristol, United Kingdom
- Kalra, Philip A., Northern Care Alliance NHS Foundation Trust Salford Care Organisation, Salford, United Kingdom
- Radresa, Olivier, Evotec International GmbH, Gottingen, Niedersachsen, Germany
- Skroblin, Philipp, Evotec International GmbH, Gottingen, Niedersachsen, Germany
- Taal, Maarten W., University of Nottingham, Nottingham, United Kingdom
- Welsh, Gavin Iain, University of Bristol, Bristol, United Kingdom
- Saleem, Moin A., University of Bristol, Bristol, United Kingdom
- Campbell, Ian Colin, University of Bristol, Bristol, United Kingdom
Group or Team Name
- Bristol Renal.
Background
Genetic risk variants have been associated with chronic kidney diseases (CKD) by univariate statistical methods. Multivariate statistics such as canonical correlation analysis (CCA) have not been investigated for CKD sub-types and may provide additional insights.
Methods
We applied CCA to our NURTuRE-CKD and Salford Kidney Study (SKS) CKD single nucleotide polymorphism (SNP) datasets. We assessed expression quantitative trait loci (eQTL) colocalisation, SNP differential gene expression and allele frequency.
Results
We identified 943 replicated SNPs in the human leukocyte antigen (HLA) region that showed significant correlation with membranous nephropathy (MN) compared to other CKD. Most SNPs were not previously reported. The 5 lead SNPs (previously unreported) were significantly more common in both MN and diabetic nephropathy Type 1 (T1D) compared to healthy controls and showed strong eQTL colocalisation with 17 genes. Of these, five genes in blood or monocytes (ATF6B, HLA-DQA1, HLA-DQB1, NOTCH4, RNF5) showed differential gene expression between MN and either healthy individuals or IgA nephropathy across 11 published Gene Expression Omnibus datasets, suggesting MN-specific expression. Differential gene expression analyses suggested that the five lead SNPs affected C4B, HLA-DQB1 and RNF5P1 expression in CKD.
Conclusion
In summary, we found previously unreported, replicated SNPs associated with MN and T1D, likely involved in altering HLA-DQB1 gene expression.
Single nucleotide polymorphisms for membranous nephropathy by canonical correlation analysis. Results for (a) NURTuRE-chronic kidney disease and (b) Salford Kidney Study. Each point is a SNP with chromosome and co-ordinates (x-axis) and -log10 CCA P-value (y-axis). The dashed line is Bonferroni-corrected 0.05 P-value.