Plasma Proteomics of Renal FunctionCitation formats

  • External authors:
  • Pamela Matías-García
  • Rory Wilson
  • Qi Guo
  • Shaza Zaghlool
  • Fadi Charchar
  • John Dormer
  • Haifa Maalmi
  • Pascal Schlosser
  • Mohamed Elhadad
  • Jana Nano
  • Sapna Sharma
  • Annette Peters
  • Alessia Fornoni
  • Dennis Mook-Kanamori
  • Juliane Winkelmann
  • John Danesh
  • Emanuele Di Angelantonio
  • Willem Ouwehand
  • Nicholas Watkins
  • Agnese Petrera
  • Johannes Graumann
  • Wolfgang Koenig
  • Kristian Hveem
  • Christian Jonasson
  • Anna Köttgen
  • Adam Butterworth
  • Marco Prunotto
  • Stefanie Hauck
  • Christian Herder
  • Karsten Suhre
  • Christian Gieger
  • Alexander Teumer
  • Melanie Waldenberger

Standard

Plasma Proteomics of Renal Function : A Trans-ethnic Meta-analysis and Mendelian Randomization Study. / Matías-García, Pamela; Wilson, Rory; Guo, Qi; Zaghlool, Shaza; Eales, James; Xu, Xiaoguang; Charchar, Fadi; Dormer, John; Maalmi, Haifa; Schlosser, Pascal; Elhadad, Mohamed; Nano, Jana; Sharma, Sapna; Peters, Annette; Fornoni, Alessia; Mook-Kanamori, Dennis; Winkelmann, Juliane; Danesh, John; Di Angelantonio, Emanuele; Ouwehand, Willem; Watkins, Nicholas; Petrera, Agnese; Graumann, Johannes; Koenig, Wolfgang; Hveem, Kristian; Jonasson, Christian; Köttgen, Anna; Butterworth, Adam; Prunotto, Marco; Hauck, Stefanie; Herder, Christian; Suhre, Karsten; Gieger, Christian; Tomaszewski, Maciej; Teumer, Alexander; Waldenberger, Melanie.

In: Journal of the American Society of Nephrology : JASN, Vol. 32, No. 7, 07.2021, p. 1747-1763.

Research output: Contribution to journalArticlepeer-review

Harvard

Matías-García, P, Wilson, R, Guo, Q, Zaghlool, S, Eales, J, Xu, X, Charchar, F, Dormer, J, Maalmi, H, Schlosser, P, Elhadad, M, Nano, J, Sharma, S, Peters, A, Fornoni, A, Mook-Kanamori, D, Winkelmann, J, Danesh, J, Di Angelantonio, E, Ouwehand, W, Watkins, N, Petrera, A, Graumann, J, Koenig, W, Hveem, K, Jonasson, C, Köttgen, A, Butterworth, A, Prunotto, M, Hauck, S, Herder, C, Suhre, K, Gieger, C, Tomaszewski, M, Teumer, A & Waldenberger, M 2021, 'Plasma Proteomics of Renal Function: A Trans-ethnic Meta-analysis and Mendelian Randomization Study', Journal of the American Society of Nephrology : JASN, vol. 32, no. 7, pp. 1747-1763. https://doi.org/10.1681/ASN.2020071070

APA

Matías-García, P., Wilson, R., Guo, Q., Zaghlool, S., Eales, J., Xu, X., Charchar, F., Dormer, J., Maalmi, H., Schlosser, P., Elhadad, M., Nano, J., Sharma, S., Peters, A., Fornoni, A., Mook-Kanamori, D., Winkelmann, J., Danesh, J., Di Angelantonio, E., ... Waldenberger, M. (2021). Plasma Proteomics of Renal Function: A Trans-ethnic Meta-analysis and Mendelian Randomization Study. Journal of the American Society of Nephrology : JASN, 32(7), 1747-1763. https://doi.org/10.1681/ASN.2020071070

Vancouver

Matías-García P, Wilson R, Guo Q, Zaghlool S, Eales J, Xu X et al. Plasma Proteomics of Renal Function: A Trans-ethnic Meta-analysis and Mendelian Randomization Study. Journal of the American Society of Nephrology : JASN. 2021 Jul;32(7):1747-1763. https://doi.org/10.1681/ASN.2020071070

Author

Matías-García, Pamela ; Wilson, Rory ; Guo, Qi ; Zaghlool, Shaza ; Eales, James ; Xu, Xiaoguang ; Charchar, Fadi ; Dormer, John ; Maalmi, Haifa ; Schlosser, Pascal ; Elhadad, Mohamed ; Nano, Jana ; Sharma, Sapna ; Peters, Annette ; Fornoni, Alessia ; Mook-Kanamori, Dennis ; Winkelmann, Juliane ; Danesh, John ; Di Angelantonio, Emanuele ; Ouwehand, Willem ; Watkins, Nicholas ; Petrera, Agnese ; Graumann, Johannes ; Koenig, Wolfgang ; Hveem, Kristian ; Jonasson, Christian ; Köttgen, Anna ; Butterworth, Adam ; Prunotto, Marco ; Hauck, Stefanie ; Herder, Christian ; Suhre, Karsten ; Gieger, Christian ; Tomaszewski, Maciej ; Teumer, Alexander ; Waldenberger, Melanie. / Plasma Proteomics of Renal Function : A Trans-ethnic Meta-analysis and Mendelian Randomization Study. In: Journal of the American Society of Nephrology : JASN. 2021 ; Vol. 32, No. 7. pp. 1747-1763.

Bibtex

@article{e95e2c761e3b4632b4012445f3dfa65d,
title = "Plasma Proteomics of Renal Function: A Trans-ethnic Meta-analysis and Mendelian Randomization Study",
abstract = "BackgroundStudies 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.",
author = "Pamela Mat{\'i}as-Garc{\'i}a and Rory Wilson and Qi Guo and Shaza Zaghlool and James Eales and Xiaoguang Xu and Fadi Charchar and John Dormer and Haifa Maalmi and Pascal Schlosser and Mohamed Elhadad and Jana Nano and Sapna Sharma and Annette Peters and Alessia Fornoni and Dennis Mook-Kanamori and Juliane Winkelmann and John Danesh and {Di Angelantonio}, Emanuele and Willem Ouwehand and Nicholas Watkins and Agnese Petrera and Johannes Graumann and Wolfgang Koenig and Kristian Hveem and Christian Jonasson and Anna K{\"o}ttgen and Adam Butterworth and Marco Prunotto and Stefanie Hauck and Christian Herder and Karsten Suhre and Christian Gieger and Maciej Tomaszewski and Alexander Teumer and Melanie Waldenberger",
note = "Funding Information: A. Butterworth reports receiving research funding from AstraZeneca, Bayer, Biogen, BioMarin, Bioverativ, Merck, Novartis, and Sanofi; and reports receiving honoraria from Novartis. A. Fornoni reports having consultancy agreements with Dimerix, Gilead, Janssen, Novartis, ONO Pharmaceutical, and Zyversa Therapeutics; reports having an ownership interest as CSO and Vice-President of L&F Health LLC., being a shareholder in River 3 Renal Corp and Zyversa Therapeutics; reports receiving research funding from Boheringer Ingelheim and Roche; reports having patents and inventions for the use of cyclodextrin for the treatment of kidney diseases, a patent for use of small molecule inducers of cholesterol efflux; reports being a scientific advisor or member of the Journal of Clinical Investigation and Kidney International; and reports having other interests/relationships as an inventor on five pending US patents and one published patent. A. Kottgen reports receiving honoraria from Sanofi Genzyme; repost being a scientific advisor or member of the American Journal of Kidney Diseases, American Kidney Fund, Journal of the American Society of Nephrology, Kidney International, and Nature Reviews Nephrology. A. Teumer reports being a scientific advisor or member of the Editorial Board of the Journal Endocrine Connections; reports having other interests/relationships as a member of the American Society of Human Genetics. C. Herder reports receiving research funding from Sanofi-Aventis; reports receiving honoraria from Lilly, Sanofi-Aventis; and reports being a scientific advisor or member of the Editorial Boards for Diabetologia, Diabetic Medicine, and Diabetes/Metabolism Research and Reviews (DMRR). C. Jon-asson reports receiving personal fees for research consultancy work from Bayer and Pfizer outside of the submitted work. E. Di Angelantonio reports receiving research funding from a British Heart Foundation research grant, a National Health Service Blood and Transplant research grant, National Institute for Health Research grant, and a United Kingdom Medical Research Council research grant; reports being a scientific advisor or member as Chair of the working group for the European Society of Cardiology Cardiovascular Risk Collaboration, Member of the World Obesity Federation and World Heart Federation Expert Group on Obesity and CVD, Member of the National Health Service Blood and Transplant Clinical Trial Unit Steering Committee, European Society of Cardiology/European Atherosclerosis Society Task Force for Guidelines on Primary Prevention of Cardiovascular Disease and Management of Dyslipidaemia, and Member of the World Health Organization Risk Chart Working Group. J. Dormer reports consultancy agreements with Royal College of Pathologists; reports being on the AstraZeneca Genomics Advisory Board (2018), International Cardiovascular and Metabolic Advisory Board for Novartis (since 2010), the International Cardiovascular and Metabolism Research and Development Portfolio Committee for Novartis, the Medical Research Council International Advisory Group (ING) member, London (since 2013), the MRC High Throughput Science {\textquoteleft}Omics Panel Member, London (since 2013); the Scientific Advisory Committee for Sanofi (since 2013), and the Steering Committee of UK Biobank (since 2011). M. Prunotto is employed by Galapagos Ltd. M. Waldenberger reports being a scientific advisor or member of the Editorial board of Genes and International Journal of Molecular Science. Q. Guo is employed by BenevolentAI. S. Zaghlool reports receiving research funding from the Qatar Foundation. W. Koenig reports having consultancy agreements with Amgen, AstraZeneca, Corvidia, DalCor, Daiichi-Sankyo, Genentech, Kowa, Novartis, Pfizer, and The Medicines Company; reports receiving research funding from Abbott, Beckmann, Roche Diagnostics, Singulex; reports receiving honoraria from Amgen, AstraZeneca, Berlin-Chemie, Bristol-Myers Squibb, Novartis, and Sanofi; reports being a scientific advisor or member of the Advisory Boards for Amgen, AstraZeneca, Corvidia, Daiichi-Sankyo, DalCor, Esperion, Genentech, Kowa, Novartis, Pfizer, The Medicines Company; and reports being an Editorial Board member for Cardiovascular Drugs and Therapy and Clinical Chemistry. J. Danesh reports Scientific Advisor or Membership with the Scientific Advisory Board of Oxford BHF Centre for Research Excellence (2020), Scientific Advisory Board for Nightingale Health (2020), Genomics Advisory Board for AstraZe-neca (2018), 2015 International Cardiovascular and Metabolism Research and Development Portfolio Committee for Novartis, MRC Global Health Group member in London (2014-16), Scientific Advisory Committee for Sanofi (2013), MRC High Throughput Science Omics panel member in London (2013), and MRC International Advisory Gro (2013). D. Roberts reports Honoraria from Wiley. All remaining authors have nothing to disclose. The HUNT part of the project re-used protein data that were originally analyzed and paid for by Somalogic Inc., CO, USA. Somalogic had no role in the design and conduct of the study; collection of phenotypic data, statistical analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. Funding Information: The KORA study was initiated and financed by the Helmholtz Zentrum Mu€nchen German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research and the State of Bavaria. This work was also supported by Weill Cornell Medicine in Qatar Biomedical Research Program, the Qatar Foundation, and Qatar National Research Fund grant NPRPC11-0115-180010 (to K. Suhre). The HUNT Study is a collaboration between HUNT Research Centre (Norwegian University of Science and Technology), Nord-Tr{\o}ndelag County Council, Central Norway Health Authority, and the Norwegian Institute of Public Health. J. Danesh is supported by the National Institute for Health Research Senior Investigator Award. RNA-sequencing experiments and kidney gene expression studies were supported by British Heart Foundation project grants PG/17/35/33001 and PG/19/16/34270, and Kidney Research UK grants RP_017_20180302 and RP_013_20190305 (to M. Tomaszewski). The German Diabetes Center is funded by the German Federal Ministry of Health (Berlin, Germany), the Ministry of Culture and Science of the state North Rhine-Westphalia (Du€sseldorf, Germany), and grants from the German Federal Ministry of Education and Research (Berlin, Germany) to the German Center for Diabetes Research. The work of A. Ko€ttgen is supported by he Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project-ID 431984000 – SFB 1453. Publisher Copyright: {\textcopyright} 2021 by the American Society of Nephrology",
year = "2021",
month = jul,
doi = "10.1681/ASN.2020071070",
language = "English",
volume = "32",
pages = "1747--1763",
journal = "Journal of the American Society of Nephrology",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "7",

}

RIS

TY - JOUR

T1 - Plasma Proteomics of Renal Function

T2 - A Trans-ethnic Meta-analysis and Mendelian Randomization Study

AU - Matías-García, Pamela

AU - Wilson, Rory

AU - Guo, Qi

AU - Zaghlool, Shaza

AU - Eales, James

AU - Xu, Xiaoguang

AU - Charchar, Fadi

AU - Dormer, John

AU - Maalmi, Haifa

AU - Schlosser, Pascal

AU - Elhadad, Mohamed

AU - Nano, Jana

AU - Sharma, Sapna

AU - Peters, Annette

AU - Fornoni, Alessia

AU - Mook-Kanamori, Dennis

AU - Winkelmann, Juliane

AU - Danesh, John

AU - Di Angelantonio, Emanuele

AU - Ouwehand, Willem

AU - Watkins, Nicholas

AU - Petrera, Agnese

AU - Graumann, Johannes

AU - Koenig, Wolfgang

AU - Hveem, Kristian

AU - Jonasson, Christian

AU - Köttgen, Anna

AU - Butterworth, Adam

AU - Prunotto, Marco

AU - Hauck, Stefanie

AU - Herder, Christian

AU - Suhre, Karsten

AU - Gieger, Christian

AU - Tomaszewski, Maciej

AU - Teumer, Alexander

AU - Waldenberger, Melanie

N1 - Funding Information: A. Butterworth reports receiving research funding from AstraZeneca, Bayer, Biogen, BioMarin, Bioverativ, Merck, Novartis, and Sanofi; and reports receiving honoraria from Novartis. A. Fornoni reports having consultancy agreements with Dimerix, Gilead, Janssen, Novartis, ONO Pharmaceutical, and Zyversa Therapeutics; reports having an ownership interest as CSO and Vice-President of L&F Health LLC., being a shareholder in River 3 Renal Corp and Zyversa Therapeutics; reports receiving research funding from Boheringer Ingelheim and Roche; reports having patents and inventions for the use of cyclodextrin for the treatment of kidney diseases, a patent for use of small molecule inducers of cholesterol efflux; reports being a scientific advisor or member of the Journal of Clinical Investigation and Kidney International; and reports having other interests/relationships as an inventor on five pending US patents and one published patent. A. Kottgen reports receiving honoraria from Sanofi Genzyme; repost being a scientific advisor or member of the American Journal of Kidney Diseases, American Kidney Fund, Journal of the American Society of Nephrology, Kidney International, and Nature Reviews Nephrology. A. Teumer reports being a scientific advisor or member of the Editorial Board of the Journal Endocrine Connections; reports having other interests/relationships as a member of the American Society of Human Genetics. C. Herder reports receiving research funding from Sanofi-Aventis; reports receiving honoraria from Lilly, Sanofi-Aventis; and reports being a scientific advisor or member of the Editorial Boards for Diabetologia, Diabetic Medicine, and Diabetes/Metabolism Research and Reviews (DMRR). C. Jon-asson reports receiving personal fees for research consultancy work from Bayer and Pfizer outside of the submitted work. E. Di Angelantonio reports receiving research funding from a British Heart Foundation research grant, a National Health Service Blood and Transplant research grant, National Institute for Health Research grant, and a United Kingdom Medical Research Council research grant; reports being a scientific advisor or member as Chair of the working group for the European Society of Cardiology Cardiovascular Risk Collaboration, Member of the World Obesity Federation and World Heart Federation Expert Group on Obesity and CVD, Member of the National Health Service Blood and Transplant Clinical Trial Unit Steering Committee, European Society of Cardiology/European Atherosclerosis Society Task Force for Guidelines on Primary Prevention of Cardiovascular Disease and Management of Dyslipidaemia, and Member of the World Health Organization Risk Chart Working Group. J. Dormer reports consultancy agreements with Royal College of Pathologists; reports being on the AstraZeneca Genomics Advisory Board (2018), International Cardiovascular and Metabolic Advisory Board for Novartis (since 2010), the International Cardiovascular and Metabolism Research and Development Portfolio Committee for Novartis, the Medical Research Council International Advisory Group (ING) member, London (since 2013), the MRC High Throughput Science ‘Omics Panel Member, London (since 2013); the Scientific Advisory Committee for Sanofi (since 2013), and the Steering Committee of UK Biobank (since 2011). M. Prunotto is employed by Galapagos Ltd. M. Waldenberger reports being a scientific advisor or member of the Editorial board of Genes and International Journal of Molecular Science. Q. Guo is employed by BenevolentAI. S. Zaghlool reports receiving research funding from the Qatar Foundation. W. Koenig reports having consultancy agreements with Amgen, AstraZeneca, Corvidia, DalCor, Daiichi-Sankyo, Genentech, Kowa, Novartis, Pfizer, and The Medicines Company; reports receiving research funding from Abbott, Beckmann, Roche Diagnostics, Singulex; reports receiving honoraria from Amgen, AstraZeneca, Berlin-Chemie, Bristol-Myers Squibb, Novartis, and Sanofi; reports being a scientific advisor or member of the Advisory Boards for Amgen, AstraZeneca, Corvidia, Daiichi-Sankyo, DalCor, Esperion, Genentech, Kowa, Novartis, Pfizer, The Medicines Company; and reports being an Editorial Board member for Cardiovascular Drugs and Therapy and Clinical Chemistry. J. Danesh reports Scientific Advisor or Membership with the Scientific Advisory Board of Oxford BHF Centre for Research Excellence (2020), Scientific Advisory Board for Nightingale Health (2020), Genomics Advisory Board for AstraZe-neca (2018), 2015 International Cardiovascular and Metabolism Research and Development Portfolio Committee for Novartis, MRC Global Health Group member in London (2014-16), Scientific Advisory Committee for Sanofi (2013), MRC High Throughput Science Omics panel member in London (2013), and MRC International Advisory Gro (2013). D. Roberts reports Honoraria from Wiley. All remaining authors have nothing to disclose. The HUNT part of the project re-used protein data that were originally analyzed and paid for by Somalogic Inc., CO, USA. Somalogic had no role in the design and conduct of the study; collection of phenotypic data, statistical analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. Funding Information: The KORA study was initiated and financed by the Helmholtz Zentrum Mu€nchen German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research and the State of Bavaria. This work was also supported by Weill Cornell Medicine in Qatar Biomedical Research Program, the Qatar Foundation, and Qatar National Research Fund grant NPRPC11-0115-180010 (to K. Suhre). The HUNT Study is a collaboration between HUNT Research Centre (Norwegian University of Science and Technology), Nord-Trøndelag County Council, Central Norway Health Authority, and the Norwegian Institute of Public Health. J. Danesh is supported by the National Institute for Health Research Senior Investigator Award. RNA-sequencing experiments and kidney gene expression studies were supported by British Heart Foundation project grants PG/17/35/33001 and PG/19/16/34270, and Kidney Research UK grants RP_017_20180302 and RP_013_20190305 (to M. Tomaszewski). The German Diabetes Center is funded by the German Federal Ministry of Health (Berlin, Germany), the Ministry of Culture and Science of the state North Rhine-Westphalia (Du€sseldorf, Germany), and grants from the German Federal Ministry of Education and Research (Berlin, Germany) to the German Center for Diabetes Research. The work of A. Ko€ttgen is supported by he Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project-ID 431984000 – SFB 1453. Publisher Copyright: © 2021 by the American Society of Nephrology

PY - 2021/7

Y1 - 2021/7

N2 - BackgroundStudies 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.

AB - BackgroundStudies 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.

U2 - 10.1681/ASN.2020071070

DO - 10.1681/ASN.2020071070

M3 - Article

C2 - 34135082

VL - 32

SP - 1747

EP - 1763

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

SN - 1046-6673

IS - 7

ER -