The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Abstract: Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10−12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10−14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10−103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10−49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10−93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10−23 and OR = 3.39, P = 5.2 × 10−82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20–37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Nature communications. - 11 (2020) , 1600, ISSN: 2041-1723

Classification and Topics

• Keyword: Autoimmunität ; Immungenetik

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2020
• Creator: Xie, Jingyuan ; Liu, Lili ; Mladkova, Nikol ; Wuttke, Matthias ; Köttgen, Anna ; Kleta, Robert ; Chen, Nan ; Kiryluk, Krzysztof

Further information

• DOI: 10.1038/s41467-020-15383-w
• URN: urn:nbn:de:bsz:25-freidok-1657654
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 14.08.2025, 11:01 AM CEST