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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; Paczek, 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.
Afiliação
  • Xie J; Department of Nephrology, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. nephroxie@163.com.
  • Liu L; Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
  • Mladkova N; Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
  • Li Y; Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
  • Ren H; Department of Nephrology, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Wang W; Department of Nephrology, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Cui Z; Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
  • Lin L; Institute of Nephrology, Peking University, Beijing, China.
  • Hu X; 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.
  • Yu X; Department of Nephrology, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Xu J; Department of Nephrology, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Liu G; Department of Nephrology, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Caliskan Y; Department of Nephrology, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Sidore C; Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
  • Balderes O; Institute of Nephrology, Peking University, Beijing, China.
  • Rosen RJ; 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.
  • Bodria M; Division of Nephrology, Department of Internal Medicine, Istanbul School of Medicine, Istanbul University, Istanbul, Turkey.
  • Zanoni F; Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato, Cagliari, Italy.
  • Zhang JY; Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
  • Krithivasan P; Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
  • Mehl K; Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
  • Marasa M; Department of Medicine and Surgery, University of Parma, Parma, Italy.
  • Khan A; Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
  • Ozay F; Nephrology Dialysis and Kidney Transplant Unit, Fundazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli studi di Milano, Milan, Italy.
  • Canetta PA; Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
  • Bomback AS; Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
  • Appel GB; Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
  • Sanna-Cherchi S; Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
  • Sampson MG; Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
  • Mariani LH; Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
  • Perkowska-Ptasinska A; Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
  • Durlik M; Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
  • Mucha K; Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
  • Moszczuk B; Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, USA.
  • Foroncewicz B; Department of Pediatrics-Nephrology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
  • Paczek L; Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Habura I; Arbor Research Collaborative for Health, Ann Arbor, MI, USA.
  • Ars E; Department of Transplantology, Nephrology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
  • Ballarin J; Department of Transplantology, Nephrology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
  • Mani LY; Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
  • Vogt B; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
  • Ozturk S; Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
  • Yildiz A; Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
  • Seyahi N; Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
  • Arikan H; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
  • Koc M; Department of Nephrology, University Hospital of Karol Marcinkowski in Zielona Góra, Zielona Góra, Poland.
  • Basturk T; Molecular Biology Laboratory and Nephrology Department, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau, Universitat Autònoma de Barcelona, REDINREN, IISCIII, Barcelona, Spain.
  • Karahan G; Molecular Biology Laboratory and Nephrology Department, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau, Universitat Autònoma de Barcelona, REDINREN, IISCIII, Barcelona, Spain.
  • Akgul SU; Department of Nephrology and Hypertension, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Sever MS; Department of Nephrology and Hypertension, Bern University Hospital, University of Bern, Bern, Switzerland.
Nat Commun ; 11(1): 1600, 2020 03 30.
Article em En | MEDLINE | ID: mdl-32231244
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glomerulonefrite Membranosa / Estudo de Associação Genômica Ampla Tipo de estudo: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glomerulonefrite Membranosa / Estudo de Associação Genômica Ampla Tipo de estudo: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China