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Journal Articles Nature Communications Year : 2020

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

Jingyuan Xie , Lili Liu , Nikol Mladkova , Yifu Li , Hong Ren (1) , Weiming Wang (2) , Zhao Cui (3, 4) , Li Lin (5) , Xiaofan Hu , Xialian Yu , Jing Xu (6) , Gang Liu (7) , Yasar Caliskan , Carlo Sidore (8, 9, 10) , Olivia Balderes , Raphael Rosen , Monica Bodria (11) , Francesca Zanoni , Jun Zhang (12) , 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
Jingyuan Xie
  • Function : Author
Lili Liu
Nikol Mladkova
  • Function : Author
Yifu Li
  • Function : Author
Xiaofan Hu
  • Function : Author
Xialian Yu
  • Function : Author
Yasar Caliskan
  • Function : Author
Olivia Balderes
  • Function : Author
Raphael Rosen
  • Function : Author
Francesca Zanoni
  • Function : Author
Jun Zhang
Priya Krithivasan
  • Function : Author
Karla Mehl
  • Function : Author
Maddalena Marasa
Atlas Khan
  • Function : Author
Fatih Ozay
Pietro Canetta
Andrew Bomback
Gerald Appel
  • Function : Author
Simone Sanna-Cherchi
Matthew Sampson
  • Function : Author
Laura Mariani
  • Function : Author
Agnieszka Perkowska-Ptasinska
  • Function : Author
Magdalena Durlik
  • Function : Author
Krzysztof Mucha
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
Savas Ozturk
  • Function : Author
Abdülmecit Yildiz
  • Function : Author
Nurhan Seyahi
Hakki Arikan
  • Function : Author
Mehmet Koc
Taner Basturk
  • Function : Author
Gonca Karahan
  • Function : Author
Sebahat Usta Akgul
Mehmet Sukru Sever
  • Function : Author
Dan Zhang
  • Function : Author
Domenico Santoro
Mario Bonomini
  • Function : Author
Francesco Londrino
  • Function : Author
Loreto Gesualdo
  • Function : Author
Jana Reiterova
  • Function : Author
Vladimir Tesar
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
Francesca Lugani
  • Function : Author
Gianmarco Ghiggeri
  • Function : Author
Isabella Pisani
  • Function : Author
Landino Allegri
  • Function : Author
Ben Sprangers
  • Function : Author
Jin-Ho Park
Belong Cho
  • Function : Author
Yon Su Kim
  • Function : Author
Dong Ki Kim
  • Function : Author
Hitoshi Suzuki
Antonio Amoroso
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
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
Eimear Kenny
  • Function : Author
Matthias Wuttke
Kai-Uwe Eckardt
  • Function : Author
Anna Köttgen
Julia Hofstra
  • Function : Author
Marieke Coenen
  • Function : Author
Lambertus Kiemeney
  • Function : Author
Shreeram Akilesh
Matthias Kretzler
Lawrence Beck
  • Function : Author
Benedicte Stengel
  • Function : Author
Hanna Debiec
  • Function : Author
Pierre Ronco
  • Function : Author
  • PersonId : 949869
Jack Wetzels
Magdalena Zoledziewska
  • Function : Author
Francesco Cucca
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
Ali Gharavi
Robert Kleta
Nan Chen
  • Function : Author
Krzysztof Kiryluk

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.

Dates and versions

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

Identifiers

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⟩
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