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The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis
J. Xie, L. Liu, N. Mladkova, Y. Li, H. Ren, W. Wang, Z. Cui, L. Lin, X. Hu, X. Yu, J. Xu, G. Liu, Y. Caliskan, C. Sidore, O. Balderes, RJ. Rosen, M. Bodria, F. Zanoni, JY. Zhang, P. Krithivasan, K. Mehl, M. Marasa, A. Khan, F. Ozay, PA. Canetta,...
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, metaanalýza, Research Support, N.I.H., Extramural, práce podpořená grantem
Perzistentní odkaz
https://www.medvik.cz/link/bmc20025131
Grantová podpora
RC2 DK116690
NIDDK NIH HHS - United States
S10 OD018522
NIH HHS - United States
S10 OD026880
NIH HHS - United States
R01 DK105124
NIDDK NIH HHS - United States
R01 DK097053
NIDDK NIH HHS - United States
R01 DK108805
NIDDK NIH HHS - United States
R01 MD009223
NIMHD NIH HHS - United States
U54 DK083912
NIDDK NIH HHS - United States
MR/J010847/1
Medical Research Council - United Kingdom
Online
Plný text
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od 2012
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od 2010-01-01
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od 2015-01-01
Open Access Digital Library
od 2015-01-01
Medline Complete (EBSCOhost)
od 2012-11-01
Health & Medicine (ProQuest)
od 2010-01-01
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- MeSH
- alely MeSH
- Asijci genetika MeSH
- běloši genetika MeSH
- celogenomová asociační studie * MeSH
- interferonové regulační faktory genetika MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- membranózní glomerulonefritida diagnóza genetika imunologie MeSH
- molekulární modely MeSH
- NF-kappa B - podjednotka p50 genetika MeSH
- receptory pro fosfolipasy A2 genetika MeSH
- sekvence aminokyselin MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
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.
3 Department of Medicine University Medical Center Hamburg Eppendorf Hamburg Germany
Cannizzaro Hospital Catania Italy
Department of Anatomic Pathology University of Washington Seattle USA
Department of Biostatistics Mailman School of Public Health Columbia University New York NY USA
Department of Medical Biology Istanbul School of Medicine Istanbul University Istanbul Turkey
Department of Medicine and Surgery University of Parma Parma Italy
Department of Medicine University of Chieti Pescara SS Annunziata Hospital Chieti Italy
Department of Nephrology and Dialysis G Brotzu Hospital Cagliari Italy
Department of Nephrology Division of Medicine University College London London UK
Department of Nephrology Juntendo University Faculty of Medicine Tokyo Japan
Department of Nephrology Radboud University Medical Center Nijmegen The Netherlands
Department of Nephrology Sisli Hamidiye Etfal Training and Research Hospital Istanbul Turkey
Department of Nephrology Uludag University Faculty of Medicine Bursa Turkey
Department of Nephrology University of Toronto Toronto General Hospital Toronto ON Canada
Department of Pediatrics Nephrology University of Michigan School of Medicine Ann Arbor MI USA
Division of Nephrology and Hypertension Mayo Clinic Rochester MN USA
Division of Nephrology Department of Medicine University of Michigan Ann Arbor MI USA
Division of Nephrology Dialysis Transplantation IRCCS Giannina Gaslini Genoa Italy
Faculty of Biology Medicine Health University of Manchester Manchester UK
Nephrology Clinic Haseki Training and Research Hospital Istanbul Turkey
Renal Unit Department of Medicine University of Verona Verona Italy
Renal Unit Royal London Hospital Barts Health Whitechapel London UK
S Andrea Hospital La Spezia Italy
San Giovanni Bosco Hospital and University of Turin Turin Italy
San Raffaele Hospital Milan Italy
Sandro Pertini Hospital Rome Italy
Sorbonne Université Pierre and Marie Curie University Paris 06 Paris France
Citace poskytuje Crossref.org
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- $a Xie, Jingyuan $u Department of Nephrology, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. nephroxie@163.com.
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- $a The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis / $c J. Xie, L. Liu, N. Mladkova, Y. Li, H. Ren, W. Wang, Z. Cui, L. Lin, X. Hu, X. Yu, J. Xu, G. Liu, Y. Caliskan, C. Sidore, O. Balderes, RJ. Rosen, M. Bodria, F. Zanoni, JY. Zhang, P. Krithivasan, K. Mehl, M. Marasa, A. Khan, F. Ozay, PA. Canetta, AS. Bomback, GB. Appel, S. Sanna-Cherchi, MG. Sampson, LH. Mariani, A. Perkowska-Ptasinska, M. Durlik, K. Mucha, B. Moszczuk, B. Foroncewicz, L. Pączek, I. Habura, E. Ars, J. Ballarin, LY. Mani, B. Vogt, S. Ozturk, A. Yildiz, N. Seyahi, H. Arikan, M. Koc, T. Basturk, G. Karahan, SU. Akgul, MS. Sever, D. Zhang, D. Santoro, M. Bonomini, F. Londrino, L. Gesualdo, J. Reiterova, V. Tesar, C. Izzi, S. Savoldi, D. Spotti, C. Marcantoni, P. Messa, M. Galliani, D. Roccatello, S. Granata, G. Zaza, F. Lugani, G. Ghiggeri, I. Pisani, L. Allegri, B. Sprangers, JH. Park, B. Cho, YS. Kim, DK. Kim, H. Suzuki, A. Amoroso, DC. Cattran, FC. Fervenza, A. Pani, P. Hamilton, S. Harris, S. Gupta, C. Cheshire, S. Dufek, N. Issler, RJ. Pepper, J. Connolly, S. Powis, D. Bockenhauer, HC. Stanescu, N. Ashman, RJF. Loos, EE. Kenny, M. Wuttke, KU. Eckardt, A. Köttgen, JM. Hofstra, MJH. Coenen, LA. Kiemeney, S. Akilesh, M. Kretzler, LH. Beck, B. Stengel, H. Debiec, P. Ronco, JFM. Wetzels, M. Zoledziewska, F. Cucca, I. Ionita-Laza, H. Lee, E. Hoxha, RAK. Stahl, P. Brenchley, F. Scolari, MH. Zhao, AG. Gharavi, R. Kleta, N. Chen, K. Kiryluk,
- 520 9_
- $a 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.
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- $a Liu, Lili $u Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Hu, Xiaofan $u Department of Nephrology, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- 700 1_
- $a Yu, Xialian $u Department of Nephrology, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- 700 1_
- $a Xu, Jing $u Department of Nephrology, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- 700 1_
- $a Liu, Gang $u Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China. Institute of Nephrology, Peking University, Beijing, China. Key Laboratory of Renal Disease, Ministry of Health of China, and Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijng, China.
- 700 1_
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- 700 1_
- $a Sidore, Carlo $u Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato, Cagliari, Italy.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Perkowska-Ptasinska, Agnieszka $u Department of Transplantology, Nephrology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Habura, Ireneusz $u Department of Nephrology, University Hospital of Karol Marcinkowski in Zielona Góra, Zielona Góra, Poland.
- 700 1_
- $a Ars, Elisabet $u Molecular Biology Laboratory and Nephrology Department, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau, Universitat Autònoma de Barcelona, REDINREN, IISCIII, Barcelona, Spain.
- 700 1_
- $a Ballarin, Jose $u Molecular Biology Laboratory and Nephrology Department, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau, Universitat Autònoma de Barcelona, REDINREN, IISCIII, Barcelona, Spain.
- 700 1_
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- 700 1_
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- 700 1_
- $a Ozturk, Savas $u Nephrology Clinic, Haseki Training and Research Hospital, Istanbul, Turkey.
- 700 1_
- $a Yildiz, Abdülmecit $u Department of Nephrology, Uludag University Faculty of Medicine, Bursa, Turkey.
- 700 1_
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- 700 1_
- $a Arikan, Hakki $u Division of Nephrology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Gesualdo, Loreto $u University of Bari, Bari, Italy.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Messa, Piergiorgio $u Nephrology Dialysis and Kidney Transplant Unit, Fundazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli studi di Milano, Milan, Italy.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Fervenza, Fernando C $u Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
- 700 1_
- $a Pani, Antonello $u Department of Nephrology and Dialysis, G. Brotzu Hospital, Cagliari, Italy.
- 700 1_
- $a Hamilton, Patrick $u Manchester Institute of Nephrology and Transplantation, Manchester University Hospitals NHS Trust, Manchester, UK.
- 700 1_
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- 700 1_
- $a Gupta, Sanjana $u Department of Nephrology, Division of Medicine, University College London, London, UK.
- 700 1_
- $a Cheshire, Chris $u Department of Nephrology, Division of Medicine, University College London, London, UK.
- 700 1_
- $a Dufek, Stephanie $u Department of Nephrology, Division of Medicine, University College London, London, UK.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Eckardt, Kai-Uwe $u Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany. Department of Nephrology and Hypertension, Friedrich-Alexander-Universität, Erlangen, Germany.
- 700 1_
- $a Köttgen, Anna $u Institute of Genetic Epidemiology, Dep. of Biometry, Epidemiology, and Medical Bioinformatics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Akilesh, Shreeram $u Department of Anatomic Pathology, University of Washington, Seattle, USA.
- 700 1_
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- 700 1_
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- 700 1_
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