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Updated: Jun 17, 2025
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Author Spotlight: Modeling an Aspect of Preeclampsia in Female Mice Using Hypoxic Human Placenta-Derived Small Extracellular Vesicles
Published on: January 26, 2024
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Proteome- and Transcriptome-Wide Genetic Analysis Identifies Biological Pathways and Candidate Drug Targets for
Maddalena Ardissino1,2,3,4, Buu Truong5,6, Eric A W Slob7,8,9,10
1British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (M.A., L.G., A.B.), University of Cambridge, United Kingdom.
Circulation. Genomic and Precision Medicine
|August 9, 2024
Summary
This study identified 18 circulating proteins associated with preeclampsia, highlighting SERPINE2, PZP, FGF5, FES, and ANP as key proteins. These findings may lead to novel targeted therapies for preeclampsia.
Area of Science:
- Genetics
- Proteomics
- Molecular Biology
Background:
- Preeclampsia is a significant global health concern, contributing to maternal and perinatal mortality.
- Current understanding of preeclampsia's biological underpinnings is limited, necessitating further research into its causal pathways.
Purpose of the Study:
- To investigate the causal relevance of circulating proteins in preeclampsia using a cross-platform proteome- and transcriptome-wide genetic analysis.
- To identify potential therapeutic targets for preeclampsia by exploring protein associations and biological pathways.
Main Methods:
- Conducted a proteome- and transcriptome-wide genetic analysis on over 2000 circulating proteins and 15,000 genes.
- Utilized large-scale genetic association data from European ancestry women with preeclampsia.
- Employed Bayesian colocalization analyses and protein interaction mapping to assess causal relationships and identify shared pathways.
Main Results:
- Identified genetic associations between 18 circulating proteins and preeclampsia.
- Found that 11 proteins were supported by gene expression data, and 9 by Bayesian colocalization.
- Highlighted SERPINE2, PZP, FGF5, FES, and ANP as proteins supported by all examined evidence, suggesting strong causal links.
Conclusions:
- Identified multiple targetable proteins involved in cardiovascular, inflammatory, and coagulation pathways relevant to preeclampsia.
- SERPINE2, PZP, FGF5, FES, and ANP are pivotal proteins with likely causal roles in preeclampsia development.
- These findings provide a foundation for developing targeted therapies to combat preeclampsia.
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