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Sekula P, Li Y, Stanescu HC, et al. Genetic risk variants for membranous nephropathy: extension of and association with other chronic kidney disease aetiologies. Nephrol Dial Transplant. 2016;32(2):325-332doi: 10.1093/ndt/gfw001.
Sekula, P., Li, Y., Stanescu, H. C., Wuttke, M., Ekici, A. B., Bockenhauer, D., Walz, G., Powis, S. H., Kielstein, J. T., Brenchley, P., Eckardt, K. U., Kronenberg, F., Kleta, R., & Köttgen, A. (2017). Genetic risk variants for membranous nephropathy: extension of and association with other chronic kidney disease aetiologies. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 32(2), 325-332. https://doi.org/10.1093/ndt/gfw001
Sekula, Peggy, et al. "Genetic risk variants for membranous nephropathy: extension of and association with other chronic kidney disease aetiologies." Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association vol. 32,2 (2017): 325-332. doi: https://doi.org/10.1093/ndt/gfw001
Sekula P, Li Y, Stanescu HC, Wuttke M, Ekici AB, Bockenhauer D, Walz G, Powis SH, Kielstein JT, Brenchley P, Eckardt KU, Kronenberg F, Kleta R, Köttgen A. Genetic risk variants for membranous nephropathy: extension of and association with other chronic kidney disease aetiologies. Nephrol Dial Transplant. 2017 Feb 01;32(2):325-332. doi: 10.1093/ndt/gfw001. Epub 2016 Feb 04. PMID: 27333618; PMCID: PMC5837679.
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Nephrol Dial Transplant. 2017 Feb 01;32(2):325-332. doi: 10.1093/ndt/gfw001. Epub 2016 Feb 04.

Genetic risk variants for membranous nephropathy: extension of and association with other chronic kidney disease aetiologies.

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

Peggy Sekula, Yong Li, Horia C Stanescu, Matthias Wuttke, Arif B Ekici, Detlef Bockenhauer, Gerd Walz, Stephen H Powis, Jan T Kielstein, Paul Brenchley, Kai-Uwe Eckardt, Florian Kronenberg, Robert Kleta, Anna Köttgen

Affiliations

  1. Department of Internal Medicine IV, Medical Center-University of Freiburg, Freiburg, Germany.
  2. Center for Medical Biometry and Medical Informatics, Medical Center-University of Freiburg, Freiburg, Germany.
  3. Centre for Nephrology, University College London, London, UK.
  4. Institute of Human Genetics, Friedrich-Alexander University, Erlangen-Nürnberg, Germany.
  5. Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
  6. Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK.
  7. Department of Nephrology and Hypertension, Friedrich-Alexander University, Erlangen-Nürnberg, Germany.
  8. Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.

PMID: 27333618 PMCID: PMC5837679 DOI: 10.1093/ndt/gfw001

Abstract

BACKGROUND: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. Previous genome-wide association studies (GWAS) of 300 000 genotyped variants identified MN-associated loci at HLA-DQA1 and PLA2R1.

METHODS: We used a combined approach of genotype imputation, GWAS, human leucocyte antigen (HLA) imputation and extension to other aetiologies of chronic kidney disease (CKD) to investigate genetic MN risk variants more comprehensively. GWAS using 9 million high-quality imputed genotypes and classical HLA alleles were conducted for 323 MN European-ancestry cases and 345 controls. Additionally, 4960 patients with different CKD aetiologies in the German Chronic Kidney Disease (GCKD) study were genotyped for risk variants at HLA-DQA1 and PLA2R1.

RESULTS: In GWAS, lead variants in known loci [rs9272729, HLA-DQA1, odds ratio (OR) = 7.3 per risk allele, P = 5.9 × 10

CONCLUSIONS: PLA2R1 and HLA-DQA1 are the predominant risk loci for MN detected by GWAS. While HLA-DQA1 risk variants show an association with other CKD aetiologies, PLA2R1 variants are specific to MN.

© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Keywords: chronic kidney disease; genome-wide association study; membranous nephropathy

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