| Title: | Identification of Circulating Proteins Associated With Blood Pressure |
| Journal: | Hypertension |
| Published: | 3 Dec 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39624895/ |
| DOI: | https://doi.org/10.1161/hypertensionaha.124.24151 |
Publication 14670
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BACKGROUND: Circulating proteins in blood are involved in various physiological processes, but their contributions to blood pressure regulation remain partially understood. In traditional observational studies, identifying circulating proteins causally associated with blood pressure is challenging because of potentially unmeasured confounding and possible reverse causality.</p>
METHODS: Two-sample Mendelian randomization analyses were conducted to estimate the causal effects of 2270 circulating proteins (data sourced from 8 genome-wide association studies) on diastolic blood pressure, systolic blood pressure, and pulse pressure. Colocalization analyses were then used to investigate whether the circulating proteins and blood pressure traits shared causal genetic variants. To further verify the findings, we subsequently performed Steiger filtering analyses, annotation of protein-altering variants, assessment of overlap between protein quantitative trait loci and expression quantitative trait loci, protein-protein interaction and functional enrichment analyses, and drug target evaluation. To provide more potential biomarkers, we further evaluated the epidemiological associations of 2923 circulating proteins with blood pressure and hypertension by cross-sectional and longitudinal analyses using individual data in the UK Biobank.</p>
RESULTS: Mendelian randomization and colocalization analyses identified 121 circulating proteins with putative causal effects on at least 1 blood pressure trait. Many of the identified proteins are enriched in the pathways relevant to blood pressure regulation, and a majority of these proteins are either known drug targets or druggable candidates.</p>
CONCLUSIONS: This study has uncovered numerous circulating proteins potentially causally associated with blood pressure, providing insights into the regulatory mechanisms of blood pressure and potential therapeutic targets to facilitate blood pressure management.</p>
10 Keywords
- Biomarkers
- Blood Pressure
- Blood Proteins
- Female
- Genome-Wide Association Study
- Humans
- Hypertension
- Male
- Mendelian Randomization Analysis
- Quantitative Trait Loci
12 Authors
- Siqi Xu
- Simin Wen
- Xizeng Zong
- Shifeng Wen
- Jianwei Zhu
- Weipeng Zheng
- Zhiqiang Wang
- Peihua Cao
- Zhijiang Liang
- Changhai Ding
- Yan Zhang
- Guangfeng Ruan
Enabling scientific discoveries that improve human health