Canonical correlation analysis identifies single nucleotide polymorphism combinations and gene expression associated with membranous nephropathy
Abstract
In membranous nephropathy (MN), an autoimmune kidney condition, univariate genome-wide association studies (GWAS) have identified Human Leucocyte Antigen ( HLA ) and M-type phospholipase A2 receptor ( PLA2R1 ) genetic risk variants. Multivariate-single nucleotide polymorphism (SNP) canonical correlation analysis (CCA) with transcriptomics analysis, can uncover additional insights within this context. We applied CCA to our National Unified Renal Translational Research Enterprise (NURTuRE)- chronic kidney disease (CKD) and Salford Kidney Study (SKS) European datasets, identifying 1095 HLA and 46 PLA2R1 SNPs showing significant MN correlation, and single-cell gene enrichment. Top SNP combinations showed greater significance in both MN by multivariate-SNP CCA, and MN and diabetic nephropathy (Type 1) by allele frequency analysis compared to healthy and non-MN groups. ATF6B , C2, CYP21A2 , and HLA-DRB1 colocalised with top HLA SNPs and showed significant differential expression in MN (published immune transcriptomics datasets). HLA-DQB1, HLA-DRB5 and RNF5 showed significant differential expression with lead SNP genotype status in MN and CKD. These previously unreported SNP and gene results are candidates for MN and potentially Type 1 diabetic nephropathy risk prediction.
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BibTeX
@article{osborne2026canonical,
title = {{Canonical correlation analysis identifies single nucleotide polymorphism combinations and gene expression associated with membranous nephropathy}},
author = {Amy J. Osborne and Samantha Hayward and Elizabeth Colby and Uwe Andag and Philip A. Kalra and Ania Koziell and Olivier Radresa and Philipp Skroblin and Maarten W. Taal and Gavin I. Welsh and Moin A. Saleem and Colin Campbell},
journal = {Communications Biology},
year = {2026},
month = nov,
doi = {10.1038/s42003-026-11211-x},
url = {https://www.nature.com/articles/s42003-026-11211-x},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Canonical correlation analysis identifies single nucleotide polymorphism combinations and gene expression associated with membranous nephropathy
AU - Amy J. Osborne
AU - Samantha Hayward
AU - Elizabeth Colby
AU - Uwe Andag
AU - Philip A. Kalra
AU - Ania Koziell
AU - Olivier Radresa
AU - Philipp Skroblin
AU - Maarten W. Taal
AU - Gavin I. Welsh
AU - Moin A. Saleem
AU - Colin Campbell
PY - 2026
DA - 2026/11/03
JO - Communications Biology
DO - 10.1038/s42003-026-11211-x
UR - https://www.nature.com/articles/s42003-026-11211-x
AB - In membranous nephropathy (MN), an autoimmune kidney condition, univariate genome-wide association studies (GWAS) have identified Human Leucocyte Antigen ( HLA ) and M-type phospholipase A2 receptor ( PLA2R1 ) genetic risk variants. Multivariate-single nucleotide polymorphism (SNP) canonical correlation analysis (CCA) with transcriptomics analysis, can uncover additional insights within this context. We applied CCA to our National Unified Renal Translational Research Enterprise (NURTuRE)- chronic kidney disease (CKD) and Salford Kidney Study (SKS) European datasets, identifying 1095 HLA and 46 PLA2R1 SNPs showing significant MN correlation, and single-cell gene enrichment. Top SNP combinations showed greater significance in both MN by multivariate-SNP CCA, and MN and diabetic nephropathy (Type 1) by allele frequency analysis compared to healthy and non-MN groups. ATF6B , C2, CYP21A2 , and HLA-DRB1 colocalised with top HLA SNPs and showed significant differential expression in MN (published immune transcriptomics datasets). HLA-DQB1, HLA-DRB5 and RNF5 showed significant differential expression with lead SNP genotype status in MN and CKD. These previously unreported SNP and gene results are candidates for MN and potentially Type 1 diabetic nephropathy risk prediction.
SN - 2399-3642
ER -