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

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

In: NAT COMMUN, Vol. 11, No. 1, 30.03.2020, p. 1600.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Xie, J, Liu, L, Mladkova, N, Li, Y, Ren, H, Wang, W, Cui, Z, Lin, L, Hu, X, Yu, X, Xu, J, Liu, G, Caliskan, Y, Sidore, C, Balderes, O, Rosen, RJ, Bodria, M, Zanoni, F, Zhang, JY, Krithivasan, P, Mehl, K, Marasa, M, Khan, A, Ozay, F, Canetta, PA, Bomback, AS, Appel, GB, Sanna-Cherchi, S, Sampson, MG, Mariani, LH, Perkowska-Ptasinska, A, Durlik, M, Mucha, K, Moszczuk, B, Foroncewicz, B, Pączek, L, Habura, I, Ars, E, Ballarin, J, Mani, L-Y, Vogt, B, Ozturk, S, Yildiz, A, Seyahi, N, Arikan, H, Koc, M, Basturk, T, Karahan, G, Akgul, SU, Sever, MS, Zhang, D, Santoro, D, Bonomini, M, Londrino, F, Gesualdo, L, Reiterova, J, Tesar, V, Izzi, C, Savoldi, S, Spotti, D, Marcantoni, C, Messa, P, Galliani, M, Roccatello, D, Granata, S, Zaza, G, Lugani, F, Ghiggeri, G, Pisani, I, Allegri, L, Sprangers, B, Park, J-H, Cho, B, Kim, YS, Kim, DK, Suzuki, H, Amoroso, A, Cattran, DC, Fervenza, FC, Pani, A, Hamilton, P, Harris, S, Gupta, S, Cheshire, C, Dufek, S, Issler, N, Pepper, RJ, Connolly, J, Powis, S, Bockenhauer, D, Stanescu, HC, Ashman, N, Loos, RJF, Kenny, EE, Wuttke, M, Eckardt, K-U, Köttgen, A, Hofstra, JM, Coenen, MJH, Kiemeney, LA, Akilesh, S, Kretzler, M, Beck, LH, Stengel, B, Debiec, H, Ronco, P, Wetzels, JFM, Zoledziewska, M, Cucca, F, Ionita-Laza, I, Lee, H, Hoxha, E, Stahl, RAK, Brenchley, P, Scolari, F, Zhao, M-H, Gharavi, AG, Kleta, R, Chen, N & Kiryluk, K 2020, 'The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis', NAT COMMUN, vol. 11, no. 1, pp. 1600. https://doi.org/10.1038/s41467-020-15383-w

APA

Xie, J., Liu, L., Mladkova, N., Li, Y., Ren, H., Wang, W., Cui, Z., Lin, L., Hu, X., Yu, X., Xu, J., Liu, G., Caliskan, Y., Sidore, C., Balderes, O., Rosen, R. J., Bodria, M., Zanoni, F., Zhang, J. Y., ... Kiryluk, K. (2020). The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis. NAT COMMUN, 11(1), 1600. https://doi.org/10.1038/s41467-020-15383-w

Vancouver

Xie J, Liu L, Mladkova N, Li Y, Ren H, Wang W et al. The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis. NAT COMMUN. 2020 Mar 30;11(1):1600. https://doi.org/10.1038/s41467-020-15383-w

Bibtex

@article{4c4b9f0f5482403d95834d94e26b6f83,
title = "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.",
keywords = "Alleles, Amino Acid Sequence, Asian Continental Ancestry Group/genetics, Case-Control Studies, European Continental Ancestry Group/genetics, Genome-Wide Association Study, Glomerulonephritis, Membranous/diagnosis, Humans, Interferon Regulatory Factors/genetics, Models, Molecular, NF-kappa B p50 Subunit/genetics, Polymorphism, Single Nucleotide, Receptors, Phospholipase A2/genetics",
author = "Jingyuan Xie and Lili Liu and Nikol Mladkova and Yifu Li and Hong Ren and Weiming Wang and Zhao Cui and Li Lin and Xiaofan Hu and Xialian Yu and Jing Xu and Gang Liu and Yasar Caliskan and Carlo Sidore and Olivia Balderes and Rosen, {Raphael J} and Monica Bodria and Francesca Zanoni and Zhang, {Jun Y} and Priya Krithivasan and Karla Mehl and Maddalena Marasa and Atlas Khan and Fatih Ozay and Canetta, {Pietro A} and Bomback, {Andrew S} and Appel, {Gerald B} and Simone Sanna-Cherchi and Sampson, {Matthew G} and Mariani, {Laura H} and Agnieszka Perkowska-Ptasinska and Magdalena Durlik and Krzysztof Mucha and Barbara Moszczuk and Bartosz Foroncewicz and Leszek P{\c a}czek and Ireneusz Habura and Elisabet Ars and Jose Ballarin and Laila-Yasmin Mani and Bruno Vogt and Savas Ozturk and Abd{\"u}lmecit Yildiz and Nurhan Seyahi and Hakki Arikan and Mehmet Koc and Taner Basturk and Gonca Karahan and Akgul, {Sebahat Usta} and Sever, {Mehmet Sukru} and Dan Zhang and Domenico Santoro and Mario Bonomini and Francesco Londrino and Loreto Gesualdo and Jana Reiterova and Vladimir Tesar and Claudia Izzi and Silvana Savoldi and Donatella Spotti and Carmelita Marcantoni and Piergiorgio Messa and Marco Galliani and Dario Roccatello and Simona Granata and Gianluigi Zaza and Francesca Lugani and GianMarco Ghiggeri and Isabella Pisani and Landino Allegri and Ben Sprangers and Jin-Ho Park and BeLong Cho and Kim, {Yon Su} and Kim, {Dong Ki} and Hitoshi Suzuki and Antonio Amoroso and Cattran, {Daniel C} and Fervenza, {Fernando C} and Antonello Pani and Patrick Hamilton and Shelly Harris and Sanjana Gupta and Chris Cheshire and Stephanie Dufek and Naomi Issler and Pepper, {Ruth J} and John Connolly and Stephen Powis and Detlef Bockenhauer and Stanescu, {Horia C} and Neil Ashman and Loos, {Ruth J F} and Kenny, {Eimear E} and Matthias Wuttke and Kai-Uwe Eckardt and Anna K{\"o}ttgen and Hofstra, {Julia M} and Coenen, {Marieke J H} and Kiemeney, {Lambertus A} and Shreeram Akilesh and Matthias Kretzler and Beck, {Lawrence H} and Benedicte Stengel and Hanna Debiec and Pierre Ronco and Wetzels, {Jack F M} and Magdalena Zoledziewska and Francesco Cucca and Iuliana Ionita-Laza and Hajeong Lee and Elion Hoxha and Stahl, {Rolf A K} and Paul Brenchley and Francesco Scolari and Ming-Hui Zhao and Gharavi, {Ali G} and Robert Kleta and Nan Chen and Krzysztof Kiryluk",
year = "2020",
month = mar,
day = "30",
doi = "10.1038/s41467-020-15383-w",
language = "English",
volume = "11",
pages = "1600",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

AU - Xie, Jingyuan

AU - Liu, Lili

AU - Mladkova, Nikol

AU - Li, Yifu

AU - Ren, Hong

AU - Wang, Weiming

AU - Cui, Zhao

AU - Lin, Li

AU - Hu, Xiaofan

AU - Yu, Xialian

AU - Xu, Jing

AU - Liu, Gang

AU - Caliskan, Yasar

AU - Sidore, Carlo

AU - Balderes, Olivia

AU - Rosen, Raphael J

AU - Bodria, Monica

AU - Zanoni, Francesca

AU - Zhang, Jun Y

AU - Krithivasan, Priya

AU - Mehl, Karla

AU - Marasa, Maddalena

AU - Khan, Atlas

AU - Ozay, Fatih

AU - Canetta, Pietro A

AU - Bomback, Andrew S

AU - Appel, Gerald B

AU - Sanna-Cherchi, Simone

AU - Sampson, Matthew G

AU - Mariani, Laura H

AU - Perkowska-Ptasinska, Agnieszka

AU - Durlik, Magdalena

AU - Mucha, Krzysztof

AU - Moszczuk, Barbara

AU - Foroncewicz, Bartosz

AU - Pączek, Leszek

AU - Habura, Ireneusz

AU - Ars, Elisabet

AU - Ballarin, Jose

AU - Mani, Laila-Yasmin

AU - Vogt, Bruno

AU - Ozturk, Savas

AU - Yildiz, Abdülmecit

AU - Seyahi, Nurhan

AU - Arikan, Hakki

AU - Koc, Mehmet

AU - Basturk, Taner

AU - Karahan, Gonca

AU - Akgul, Sebahat Usta

AU - Sever, Mehmet Sukru

AU - Zhang, Dan

AU - Santoro, Domenico

AU - Bonomini, Mario

AU - Londrino, Francesco

AU - Gesualdo, Loreto

AU - Reiterova, Jana

AU - Tesar, Vladimir

AU - Izzi, Claudia

AU - Savoldi, Silvana

AU - Spotti, Donatella

AU - Marcantoni, Carmelita

AU - Messa, Piergiorgio

AU - Galliani, Marco

AU - Roccatello, Dario

AU - Granata, Simona

AU - Zaza, Gianluigi

AU - Lugani, Francesca

AU - Ghiggeri, GianMarco

AU - Pisani, Isabella

AU - Allegri, Landino

AU - Sprangers, Ben

AU - Park, Jin-Ho

AU - Cho, BeLong

AU - Kim, Yon Su

AU - Kim, Dong Ki

AU - Suzuki, Hitoshi

AU - Amoroso, Antonio

AU - Cattran, Daniel C

AU - Fervenza, Fernando C

AU - Pani, Antonello

AU - Hamilton, Patrick

AU - Harris, Shelly

AU - Gupta, Sanjana

AU - Cheshire, Chris

AU - Dufek, Stephanie

AU - Issler, Naomi

AU - Pepper, Ruth J

AU - Connolly, John

AU - Powis, Stephen

AU - Bockenhauer, Detlef

AU - Stanescu, Horia C

AU - Ashman, Neil

AU - Loos, Ruth J F

AU - Kenny, Eimear E

AU - Wuttke, Matthias

AU - Eckardt, Kai-Uwe

AU - Köttgen, Anna

AU - Hofstra, Julia M

AU - Coenen, Marieke J H

AU - Kiemeney, Lambertus A

AU - Akilesh, Shreeram

AU - Kretzler, Matthias

AU - Beck, Lawrence H

AU - Stengel, Benedicte

AU - Debiec, Hanna

AU - Ronco, Pierre

AU - Wetzels, Jack F M

AU - Zoledziewska, Magdalena

AU - Cucca, Francesco

AU - Ionita-Laza, Iuliana

AU - Lee, Hajeong

AU - Hoxha, Elion

AU - Stahl, Rolf A K

AU - Brenchley, Paul

AU - Scolari, Francesco

AU - Zhao, Ming-Hui

AU - Gharavi, Ali G

AU - Kleta, Robert

AU - Chen, Nan

AU - Kiryluk, Krzysztof

PY - 2020/3/30

Y1 - 2020/3/30

N2 - 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.

AB - 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.

KW - Alleles

KW - Amino Acid Sequence

KW - Asian Continental Ancestry Group/genetics

KW - Case-Control Studies

KW - European Continental Ancestry Group/genetics

KW - Genome-Wide Association Study

KW - Glomerulonephritis, Membranous/diagnosis

KW - Humans

KW - Interferon Regulatory Factors/genetics

KW - Models, Molecular

KW - NF-kappa B p50 Subunit/genetics

KW - Polymorphism, Single Nucleotide

KW - Receptors, Phospholipase A2/genetics

U2 - 10.1038/s41467-020-15383-w

DO - 10.1038/s41467-020-15383-w

M3 - SCORING: Journal article

C2 - 32231244

VL - 11

SP - 1600

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -