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

Jingyuan Xie; Lili Liu; Nikol Mladkova; Yifu Li; Hong Ren; Weiming Wang; Zhao Cui; Li Lin; Xiaofan Hu; Xialian Yu; Jing Xu; Gang Liu; Yasar Caliskan; Carlo Sidore; Olivia Balderes; Raphael Rosen; Monica Bodria; Francesca Zanoni; Jun Zhang; Priya Krithivasan; Karla Mehl; Maddalena Marasa; Atlas Khan; Fatih Ozay; Pietro Canetta; Andrew Bomback; Gerald Appel; Simone Sanna-Cherchi; Matthew Sampson; Laura Mariani; Agnieszka Perkowska-Ptasinska; Magdalena Durlik; Krzysztof Mucha; Barbara Moszczuk; Bartosz Foroncewicz; Leszek Pączek; Ireneusz Habura; Elisabet Ars; Jose Ballarin; Laila-Yasmin Mani; Bruno Vogt; Savas Ozturk; Abdülmecit Yildiz; Nurhan Seyahi; Hakki Arikan; Mehmet Koc; Taner Basturk; Gonca Karahan; Sebahat Usta Akgul; Mehmet Sukru Sever; Dan Zhang; Domenico Santoro; Mario Bonomini; Francesco Londrino; Loreto Gesualdo; Jana Reiterova; Vladimir Tesar; Claudia Izzi; Silvana Savoldi; Donatella Spotti; Carmelita Marcantoni; Piergiorgio Messa; Marco Galliani; Dario Roccatello; Simona Granata; Gianluigi Zaza; Francesca Lugani; Gianmarco Ghiggeri; Isabella Pisani; Landino Allegri; Ben Sprangers; Jin-Ho Park; Belong Cho; Yon Su Kim; Dong Ki Kim; Hitoshi Suzuki; Antonio Amoroso; Daniel Cattran; Fernando Fervenza; Antonello Pani; Patrick Hamilton; Shelly Harris; Sanjana Gupta; Chris Cheshire; Stephanie Dufek; Naomi Issler; Ruth Pepper; John Connolly; Stephen Powis; Detlef Bockenhauer; Horia Stanescu; Neil Ashman; Ruth Loos; Eimear Kenny; Matthias Wuttke; Kai-Uwe Eckardt; Anna Köttgen; Julia Hofstra; Marieke Coenen; Lambertus Kiemeney; Shreeram Akilesh; Matthias Kretzler; Lawrence Beck; Benedicte Stengel; Hanna Debiec; Pierre Ronco; Jack Wetzels; Magdalena Zoledziewska; Francesco Cucca; Iuliana Ionita-Laza; Hajeong Lee; Elion Hoxha; Rolf Stahl; Paul Brenchley; Francesco Scolari; Ming-Hui Zhao; Ali Gharavi; Robert Kleta; Nan Chen; Krzysztof Kiryluk

doi:10.1038/s41467-020-15383-w

Journal Articles Nature Communications Year : 2020

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

, , , , (1) , (2) , (3, 4) , (5) , , , (6) , (7) , , (8, 9, 10) , , , (11) , , (12) , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

1
2
3
4
5
6
7
8
9
10
11
12

Jingyuan Xie

Function : Author

Lili Liu

Function : Author
PersonId : 1210104
ORCID : 0000-0002-2622-9669

Nikol Mladkova

Function : Author

Yifu Li

Function : Author

Hong Ren

Function : Author

Queen Mary University of London

Weiming Wang

Function : Author

Nanjing Institute of Geology and Palaeontology

Zhao Cui

Function : Author

Peking University [Beijing]

Renal Division [Beijing, China]

Li Lin

Function : Author

Nanjing Institute of Geology and Palaeontology

Xiaofan Hu

Function : Author

Xialian Yu

Function : Author

Jing Xu

Function : Author

Shandong Agricultural University

Gang Liu

Function : Author

State Key Lab. of Information Engineering in Surveying, Mapping and Remote Sensing

Yasar Caliskan

Function : Author

Carlo Sidore

Function : Author

Michigan State University [East Lansing]

Istituto di Virologia Vegetale

Università degli Studi di Sassari = University of Sassari [Sassari]

Olivia Balderes

Function : Author

Raphael Rosen

Function : Author

Monica Bodria

Function : Author

IRCCS Istituto Giannina Gaslini [Genoa, Italy]

Francesca Zanoni

Function : Author

Jun Zhang

Function : Author
PersonId : 1210105
ORCID : 0000-0003-4996-8699

Xi'an Jiaotong University

Priya Krithivasan

Function : Author

Karla Mehl

Function : Author

Maddalena Marasa

Function : Author
PersonId : 1210106
ORCID : 0000-0003-0712-2329

Atlas Khan

Function : Author

Fatih Ozay

Function : Author
PersonId : 1210107
ORCID : 0000-0002-1383-7892

Pietro Canetta

Function : Author
PersonId : 1210108
ORCID : 0000-0003-1130-5486

Andrew Bomback

Function : Author
PersonId : 1210109
ORCID : 0000-0001-5449-1667

Gerald Appel

Function : Author

Simone Sanna-Cherchi

Function : Author
PersonId : 1210110
ORCID : 0000-0002-6185-948X

Matthew Sampson

Function : Author

Laura Mariani

Function : Author

Agnieszka Perkowska-Ptasinska

Function : Author

Magdalena Durlik

Function : Author

Krzysztof Mucha

Function : Author
PersonId : 1210111
ORCID : 0000-0002-6613-7638

Barbara Moszczuk

Function : Author

Bartosz Foroncewicz

Function : Author

Leszek Pączek

Function : Author

Ireneusz Habura

Function : Author

Elisabet Ars

Function : Author

Jose Ballarin

Function : Author

Laila-Yasmin Mani

Function : Author

Bruno Vogt

Function : Author
PersonId : 802464
ORCID : 0000-0002-1548-6387

Savas Ozturk

Function : Author

Abdülmecit Yildiz

Function : Author

Nurhan Seyahi

Function : Author
PersonId : 1210112
ORCID : 0000-0001-7427-618X

Hakki Arikan

Function : Author

Mehmet Koc

Function : Author
PersonId : 1210113
ORCID : 0000-0002-1433-8403

Taner Basturk

Function : Author

Gonca Karahan

Function : Author

Sebahat Usta Akgul

Function : Author
PersonId : 1210114
ORCID : 0000-0003-0176-3344

Mehmet Sukru Sever

Function : Author

Dan Zhang

Function : Author

Domenico Santoro

Function : Author
PersonId : 1210115
ORCID : 0000-0002-4279-6559

Mario Bonomini

Function : Author

Francesco Londrino

Function : Author

Loreto Gesualdo

Function : Author

Jana Reiterova

Function : Author

Vladimir Tesar

Function : Author
PersonId : 1210116
ORCID : 0000-0001-6982-0689

Claudia Izzi

Function : Author

Silvana Savoldi

Function : Author

Donatella Spotti

Function : Author

Carmelita Marcantoni

Function : Author

Piergiorgio Messa

Function : Author

Marco Galliani

Function : Author

Dario Roccatello

Function : Author

Simona Granata

Function : Author

Gianluigi Zaza

Function : Author
PersonId : 1210117
ORCID : 0000-0002-6004-6196

Francesca Lugani

Function : Author

Gianmarco Ghiggeri

Function : Author

Isabella Pisani

Function : Author

Landino Allegri

Function : Author

Ben Sprangers

Function : Author

Jin-Ho Park

Function : Author
PersonId : 1210118
ORCID : 0000-0002-3942-6813

Belong Cho

Function : Author

Yon Su Kim

Function : Author

Dong Ki Kim

Function : Author

Hitoshi Suzuki

Function : Author
PersonId : 1210119
ORCID : 0000-0002-1901-2111

Antonio Amoroso

Function : Author
PersonId : 1210120
ORCID : 0000-0002-9437-9407

Daniel Cattran

Function : Author

Fernando Fervenza

Function : Author

Antonello Pani

Function : Author

Patrick Hamilton

Function : Author

Shelly Harris

Function : Author

Sanjana Gupta

Function : Author

Chris Cheshire

Function : Author

Stephanie Dufek

Function : Author
PersonId : 1210121
ORCID : 0000-0002-6323-6673

Naomi Issler

Function : Author

Ruth Pepper

Function : Author

John Connolly

Function : Author

Stephen Powis

Function : Author

Detlef Bockenhauer

Function : Author

Horia Stanescu

Function : Author

Neil Ashman

Function : Author

Ruth Loos

Function : Author
PersonId : 1210122
ORCID : 0000-0002-8532-5087

Eimear Kenny

Function : Author

Matthias Wuttke

Function : Author
PersonId : 1210123
ORCID : 0000-0003-3420-5082

Kai-Uwe Eckardt

Function : Author

Anna Köttgen

Function : Author
PersonId : 1210124
ORCID : 0000-0002-4671-3714

Julia Hofstra

Function : Author

Marieke Coenen

Function : Author

Lambertus Kiemeney

Function : Author

Shreeram Akilesh

Function : Author
PersonId : 1210125
ORCID : 0000-0003-3152-7991

Matthias Kretzler

Function : Author
PersonId : 1210126
ORCID : 0000-0003-4064-0582

Lawrence Beck

Function : Author

Benedicte Stengel

Function : Author

Hanna Debiec

Function : Author

Pierre Ronco

Function : Author
PersonId : 949869

Jack Wetzels

Function : Author
PersonId : 1210103
ORCID : 0000-0002-0650-6921

Magdalena Zoledziewska

Function : Author

Francesco Cucca

Function : Author
PersonId : 1176134
ORCID : 0000-0002-7414-1995

Iuliana Ionita-Laza

Function : Author

Hajeong Lee

Function : Author

Elion Hoxha

Function : Author

Rolf Stahl

Function : Author

Paul Brenchley

Function : Author

Francesco Scolari

Function : Author

Ming-Hui Zhao

Function : Author
PersonId : 1210127
ORCID : 0000-0003-3340-3108

Ali Gharavi

Function : Author
PersonId : 1210128
ORCID : 0000-0003-2801-233X

Robert Kleta

Function : Author
PersonId : 1210129
ORCID : 0000-0002-0228-8656

Nan Chen

Function : Author

Krzysztof Kiryluk

Function : Author
PersonId : 1210130
ORCID : 0000-0002-5047-6715

Abstract

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.

Domains

Urology and Nephrology

Pierre RONCO : Connect in order to contact the contributor

https://hal.sorbonne-universite.fr/hal-03915879

Submitted on : Thursday, December 29, 2022-10:40:58 PM

Last modification on : Wednesday, November 27, 2024-11:29:30 AM

Dates and versions

hal-03915879 , version 1 (29-12-2022)

Identifiers

HAL Id : hal-03915879 , version 1
DOI : 10.1038/s41467-020-15383-w

Cite

Jingyuan Xie, Lili Liu, Nikol Mladkova, Yifu Li, Hong Ren, et al.. The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis. Nature Communications, 2020, 11 (1), pp.1600. ⟨10.1038/s41467-020-15383-w⟩. ⟨hal-03915879⟩

Export

BibTeX XML-TEI Dublin Core DC Terms EndNote DataCite

Collections

U1155 SORBONNE-UNIVERSITE SU-MEDECINE ANR

19 View

0 Download

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

Abstract

Domains

Dates and versions

Identifiers

Cite

Export

Collections

Altmetric

Share