Revealing the role of the human blood plasma proteome in obesity using genetic drivers

Zaghlool, Shaza B.; Sharma, Sapna; Molnar, Megan; Matías‐García, Pamela R.; Elhadad, Mohamed A.; Waldenberger, Mélanie; Peters, Annette; Rathmann, Wolfgang; Graumann, Johannes; Gieger, Christian; Grallert, Harald; Suhre, Karsten

doi:10.1038/s41467-021-21542-4

Cited by 63 publications

(83 citation statements)

References 82 publications

(84 reference statements)

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“…IGFBP-1 plays an important role in diabetes and diabetic nephropathy. IGFBP-1 is associated closely with obesity and insulin resistance ( Maddux et al, 2006 ; Rajwani et al, 2012 ; Bernardo et al, 2015 ; Zaghlool et al, 2021 ). The diagnosis, treatment and prognosis of type 1 and type 2 diabetes mellitus are very different, and the mechanisms of diabetic kidney disease (DKD) are still unclear, the treatment of DKD is a difficulty in clinic.…”

Section: Igfbp-1mentioning

confidence: 99%

Insulin-Like Growth Factor Binding Proteins in Kidney Disease

Wang

Chi

et al. 2021

Front. Pharmacol.

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The seven members of the insulin-like growth factor (IGF) binding protein family (IGFBPs) were initially considered to be the regulatory proteins of IGFs in the blood circulation, mainly as the subsequent reserve for bidirectional regulation of IGF function during environmental changes. However, in recent years, IGFBPs has been found to have many functions independent of IGFs. The role of IGFBPs in regulating transcription, inducing cell migration and apoptosis is closely related to the occurrence and development of kidney disease. IGFBP-1, IGFBP-3, IGFBP-4 are closely associated with diabetes and diabetic nephropathy. IGFBP-3, IGFBP-4, IGFBP-5, IGFBP-6 are involved in different kidney disease such as diabetes, FSGS and CKD physiological process as apoptosis proteins, IGFBP-7 has been used in clinical practice as a biomarker for early diagnosis and prognosis of AKI. This review focuses on the differential expression and pathogenesis of IGFBPs in kidney disease.

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Section: Igfbp-1mentioning

confidence: 99%

Insulin-Like Growth Factor Binding Proteins in Kidney Disease

Wang

Chi

et al. 2021

Front. Pharmacol.

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“…Sensitivity analyses were also run using eGFR cys (derived from the CKD Epidemiology Collaboration equation using cystatin C). 13…”

Section: Outcome Definitionsmentioning

confidence: 99%

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

Matías‐García

Wilson

Guo

et al. 2021

JASN

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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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“…Wingo et al (2021) integrated 376 human brain proteomes with GWAS data from 455,528 individuals in which 13 coding genes were found causal for protein levels as well to be correlated with Alzheimer's disease, neuroticism, and Parkinson disease (Wingo et al, 2021). Zaghlool et al (2021) studied the association between 1,000 plasma proteins and body mass index over 4,600 participants where 21 proteins in pathways of adiposity were found to be causal drivers in obesity-associated pathologies (Zaghlool et al, 2021).…”

Section: Integration With Genomic Datamentioning

confidence: 99%

Towards Building a Quantitative Proteomics Toolbox in Precision Medicine: A Mini-Review

et al. 2021

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Precision medicine as a framework for disease diagnosis, treatment, and prevention at the molecular level has entered clinical practice. From the start, genetics has been an indispensable tool to understand and stratify the biology of chronic and complex diseases in precision medicine. However, with the advances in biomedical and omics technologies, quantitative proteomics is emerging as a powerful technology complementing genetics. Quantitative proteomics provide insight about the dynamic behaviour of proteins as they represent intermediate phenotypes. They provide direct biological insights into physiological patterns, while genetics accounting for baseline characteristics. Additionally, it opens a wide range of applications in clinical diagnostics, treatment stratification, and drug discovery. In this mini-review, we discuss the current status of quantitative proteomics in precision medicine including the available technologies and common methods to analyze quantitative proteomics data. Furthermore, we highlight the current challenges to put quantitative proteomics into clinical settings and provide a perspective to integrate proteomics data with genomics data for future applications in precision medicine.

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Revealing the role of the human blood plasma proteome in obesity using genetic drivers

Cited by 63 publications

References 82 publications

Insulin-Like Growth Factor Binding Proteins in Kidney Disease

Insulin-Like Growth Factor Binding Proteins in Kidney Disease

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

Towards Building a Quantitative Proteomics Toolbox in Precision Medicine: A Mini-Review

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