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

Xie, Jingyuan; Liu, Lili; Mladkova, Nikol; Li, Yifu; Ren, Hong; Wang, Weiming; Cui, Zhao; Lin, Li; Hu, Xiaofan; Yu, Xialian; Xu, Jing; Liu, Gang; Caliskan, Yasar; Sidore, Carlo; Balderes, Olivia; Rosen, Raphael; Bodria, Monica; Zanoni, Francesca; Zhang, Yun; Krithivasan, Priya; ... (2020). The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis. Nature communications, 11(1), p. 1600. Nature Publishing Group 10.1038/s41467-020-15383-w

s41467-020-15383-w.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (2MB) | Preview

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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Mani, Laila-Yasmin, Vogt, Bruno


600 Technology > 610 Medicine & health




Nature Publishing Group




Laila-Yasmin Mani

Date Deposited:

15 Mar 2021 15:38

Last Modified:

05 Dec 2022 15:48

Publisher DOI:


PubMed ID:





Actions (login required)

Edit item Edit item
Provide Feedback