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Matias-Garcia, P.R. ; Wilson, R. ; Guo, Q.* ; Zaghlool, S.* ; Eales, J.* ; Xu, X.* ; Charchar, F.J.* ; Dormer, J.* ; Maalmi, H.* ; Schlosser, P.* ; Elhadad, M.A. ; Nano, J. ; Sharma, S. ; Peters, A. ; Fornoni, A.* ; Mook-Kanamori, D.* ; Winkelmann, J. ; Danesh, J.* ; di Angelantonio, E.* ; Ouwehand, W.* ; Watkins, N.* ; Roberts, D.* ; Petrera, A. ; Graumann, J.* ; Koenig, W.* ; Hveem, K.* ; Jonasson, C.* ; Köttgen, A.* ; Butterworth, A.* ; Prunotto, M.* ; Hauck, S.M. ; Herder, C.* ; Suhre, K.* ; Gieger, C. ; Tomaszewski, M.* ; Teumer, A.* ; Waldenberger, M.

Plasma proteomics of renal function: A trans-ethnic metaanalysis and Mendelian randomization study.

J. Am. Soc. Nephrol. 32, 1747-1763 (2021)
Publ. Version/Full Text Postprint DOI PMC
Open Access Green
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Chronic Kidney-disease; Causal Inference; Instruments; Protein; Complementarity; Classification; Integration; Technology; Mechanisms; Biomarkers
ISSN (print) / ISBN 1046-6673
e-ISSN 1533-3450
Journal Journal of the American Society of Nephrology
Quellenangaben Volume: 32, Issue: 7, Pages: 1747-1763 Article Number: , Supplement: ,
Publisher American Society of Nephrology
Publishing Place 1725 I St, Nw Ste 510, Washington, Dc 20006 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Neurogenomics (ING)
CF Metabolomics & Proteomics (CF-MPC)