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Plasma Proteomics of Renal Function: A Transethnic Meta-Analysis and Mendelian Randomization Study.
Matías-García, Pamela R; Wilson, Rory; Guo, Qi; Zaghlool, Shaza B; Eales, James M; Xu, Xiaoguang; Charchar, Fadi J; Dormer, John; Maalmi, Haifa; Schlosser, Pascal; Elhadad, Mohamed A; Nano, Jana; Sharma, Sapna; Peters, Annette; Fornoni, Alessia; Mook-Kanamori, Dennis O; Winkelmann, Juliane; Danesh, John; Di Angelantonio, Emanuele; Ouwehand, Willem H; Watkins, Nicholas A; Roberts, David J; Petrera, Agnese; Graumann, Johannes; Koenig, Wolfgang; Hveem, Kristian; Jonasson, Christian; Köttgen, Anna; Butterworth, Adam; Prunotto, Marco; Hauck, Stefanie M; Herder, Christian; Suhre, Karsten; Gieger, Christian; Tomaszewski, Maciej; Teumer, Alexander; Waldenberger, Melanie.
Afiliación
  • Matías-García PR; Research Unit Molecular Epidemiology, German Research Center for Environmental Health, Neuherberg, Germany.
  • Wilson R; Institute of Epidemiology, German Research Center for Environmental Health, Neuherberg, Germany.
  • Guo Q; TUM School of Medicine, Technical University of Munich, Munich, Germany.
  • Zaghlool SB; German Center for Cardiovascular Research, Munich, Germany.
  • Eales JM; Research Unit Molecular Epidemiology, German Research Center for Environmental Health, Neuherberg, Germany.
  • Xu X; Institute of Epidemiology, German Research Center for Environmental Health, Neuherberg, Germany.
  • Charchar FJ; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
  • Dormer J; Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Doha, Qatar.
  • Maalmi H; Division of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom.
  • Schlosser P; Division of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom.
  • Elhadad MA; School of Health and Life Sciences, Federation University Australia, Ballarat, Australia.
  • Nano J; Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.
  • Sharma S; Department of Physiology, University of Melbourne, Melbourne, Australia.
  • Peters A; Department of Cellular Pathology, University Hospitals of Leicester National Health Service Trust, Leicester, United Kingdom.
  • Fornoni A; Institute for Clinical Diabetology, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • Mook-Kanamori DO; German Center for Diabetes Research, München-Neuherberg, Germany.
  • Winkelmann J; Department of Data-Driven Medicine, Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
  • Danesh J; Research Unit Molecular Epidemiology, German Research Center for Environmental Health, Neuherberg, Germany.
  • Di Angelantonio E; Institute of Epidemiology, German Research Center for Environmental Health, Neuherberg, Germany.
  • Ouwehand WH; German Center for Cardiovascular Research, Munich, Germany.
  • Watkins NA; Institute of Epidemiology, German Research Center for Environmental Health, Neuherberg, Germany.
  • Roberts DJ; German Center for Diabetes Research, München-Neuherberg, Germany.
  • Petrera A; Research Unit Molecular Epidemiology, German Research Center for Environmental Health, Neuherberg, Germany.
  • Graumann J; Institute of Epidemiology, German Research Center for Environmental Health, Neuherberg, Germany.
  • Koenig W; Institute of Epidemiology, German Research Center for Environmental Health, Neuherberg, Germany.
  • Hveem K; German Center for Cardiovascular Research, Munich, Germany.
  • Jonasson C; German Center for Diabetes Research, München-Neuherberg, Germany.
  • Köttgen A; Department of Medicine, Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida.
  • Butterworth A; Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands.
  • Prunotto M; Institute of Neurogenomics, German Research Center for Environmental Health, Neuherberg, Germany.
  • Hauck SM; Department of Neurogenetics and Institute of Human Genetics, Technical University of Munich, Munich, Germany.
  • Herder C; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
  • Suhre K; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, United Kingdom.
  • Gieger C; National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, United Kingdom.
  • Tomaszewski M; National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge and Cambridge University Hospitals, Cambridge, United Kingdom.
  • Teumer A; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, United Kingdom.
  • Waldenberger M; Department of Human Genetics, Wellcome Sanger Institute, Hinxton, United Kingdom.
J Am Soc Nephrol ; 32(7): 1747-1763, 2021 Jul.
Article en En | MEDLINE | ID: mdl-34135082
BACKGROUND: Studies on the relationship between renal function and the human plasma proteome have identified several potential biomarkers. However, investigations have been conducted largely in European populations, and causality of the associations between plasma proteins and kidney function has never been addressed. METHODS: A cross-sectional study of 993 plasma proteins among 2882 participants in four studies of European and admixed ancestries (KORA, INTERVAL, HUNT, QMDiab) identified transethnic associations between eGFR/CKD and proteomic biomarkers. For the replicated associations, two-sample bidirectional Mendelian randomization (MR) was used to investigate potential causal relationships. Publicly available datasets and transcriptomic data from independent studies were used to examine the association between gene expression in kidney tissue and eGFR. RESULTS: In total, 57 plasma proteins were associated with eGFR, including one novel protein. Of these, 23 were additionally associated with CKD. The strongest inferred causal effect was the positive effect of eGFR on testican-2, in line with the known biological role of this protein and the expression of its protein-coding gene (SPOCK2) in renal tissue. We also observed suggestive evidence of an effect of melanoma inhibitory activity (MIA), carbonic anhydrase III, and cystatin-M on eGFR. CONCLUSIONS: In a discovery-replication setting, we identified 57 proteins transethnically associated with eGFR. The revealed causal relationships are an important stepping stone in establishing testican-2 as a clinically relevant physiological marker of kidney disease progression, and point to additional proteins warranting further investigation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Clinical_trials / Observational_studies / Risk_factors_studies / Systematic_reviews Idioma: En Revista: J Am Soc Nephrol Asunto de la revista: NEFROLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Clinical_trials / Observational_studies / Risk_factors_studies / Systematic_reviews Idioma: En Revista: J Am Soc Nephrol Asunto de la revista: NEFROLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Alemania
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