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  Plasma Proteomics of Renal Function: A Transethnic Meta-Analysis and Mendelian Randomization Study

Matias-Garcia, P. R., Wilson, R., Guo, Q., Zaghlool, S. B., Eales, J. M., Xu, X., et al. (2021). Plasma Proteomics of Renal Function: A Transethnic Meta-Analysis and Mendelian Randomization Study. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 32(7), 1747-1763. doi:10.1681/ASN.2020071070.

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Matias-Garcia, Pamela R., Author
Wilson, Rory, Author
Guo, Qi, Author
Zaghlool, Shaza B., Author
Eales, James M., Author
Xu, Xiaoguang, Author
Charchar, Fadi J., Author
Dormer, John, Author
Maalmi, Haifa, Author
Schlosser, Pascal, Author
Elhadad, Mohamed A., Author
Nano, Jana, Author
Sharma, Sapna, Author
Peters, Annette, Author
Fornoni, Alessia, Author
Mook-Kanamori, Dennis O., Author
Winkelmann, Juliane, Author
Danesh, John, Author
Di Angelantonio, Emanuele, Author
Ouwehand, Willem H., Author
Watkins, Nicholas A., AuthorRoberts, David J., AuthorPetrera, Agnese, AuthorGraumann, Johannes1, Author              Koenig, Wolfgang, AuthorHveem, Kristian, AuthorJonasson, Christian, AuthorKoettgen, Anna, AuthorButterworth, Adam, AuthorPrunotto, Marco, AuthorHauck, Stefanie, AuthorHerder, Christian, AuthorSuhre, Karsten, AuthorGieger, Christian, AuthorTomaszewski, Maciej, AuthorTeumer, Alexander, AuthorWaldenberger, Melanie, Author more..
Affiliations:
1Biomolecular Mass Spectrometry, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591705              

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 Abstract: 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 Across-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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 Dates: 2021-06-162021-07
 Publication Status: Published in print
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 Identifiers: ISI: 000753511400018
DOI: 10.1681/ASN.2020071070
PMID: 34135082
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Title: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Source Genre: Journal
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Pages: - Volume / Issue: 32 (7) Sequence Number: - Start / End Page: 1747 - 1763 Identifier: ISSN: 1046-6673