UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Xie, J; Liu, L; Mladkova, N; Li, Y; Ren, H; Wang, W; Cui, Z; ... Kiryluk, K; + view all (2020) The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis. Nature Communications , 11 (1) , Article 1600. 10.1038/s41467-020-15383-w. Green open access

[thumbnail of s41467-020-15383-w.pdf]
Preview
Text
s41467-020-15383-w.pdf - Published Version

Download (2MB) | Preview

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.

Type: Article
Title: The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-020-15383-w
Publisher version: https://doi.org/10.1038/s41467-020-15383-w
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10094590
Downloads since deposit
28Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item