Dataset Information

Plasma Proteomics of Renal Function: A Trans-ethnic Meta-analysis and Mendelian Randomization Study.

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

A cross-sectional study of 993 plasma proteins among 2,882 participants in four studies of European and admixed ancestries (KORA, INTERVAL, HUNT, QMDiab) identified trans-ethnic 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

Fifty-seven plasma proteins were associated with eGFR, including one novel protein. Twenty-three of these 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 trans-ethnically 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.

SUBMITTER: Matias-Garcia P

PROVIDER: S-EPMC8425654 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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

Matías-García Pamela R PR Wilson Rory R Guo Qi Q Zaghlool Shaza B SB Eales James M JM Xu Xiaoguang X Charchar Fadi J FJ Dormer John J Maalmi Haifa H Schlosser Pascal P Elhadad Mohamed A MA Nano Jana J Sharma Sapna S Peters Annette A Fornoni Alessia A Mook-Kanamori Dennis O DO Winkelmann Juliane J Danesh John J Di Angelantonio Emanuele E Ouwehand Willem H WH Watkins Nicholas A NA Roberts David J DJ Petrera Agnese A Graumann Johannes J Koenig Wolfgang W Hveem Kristian K Jonasson Christian C Köttgen Anna A Butterworth Adam A Prunotto Marco M Hauck Stefanie M SM Herder Christian C Suhre Karsten K Gieger Christian C Tomaszewski Maciej M Teumer Alexander A Teumer Alexander A Waldenberger Melanie M

Journal of the American Society of Nephrology : JASN 20210616 7

<h4>Background</h4>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.<h4>Methods</h4>A cross-sectional study of 993 plasma proteins among 2882 participants in four studies of European and admixed ancestries (KORA, INTERVAL, HUNT, QMDiab) ident ...[more]

PMID: 34135082

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