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Plasma proteins and coronary atherosclerosis: A Mendelian randomization study
Henan Pan1,2, Zongkai Wu2, Yaran Gao2
1Department of Graduate School, Hebei Medical University, Shijiazhuang, Hebei, China.
Insights
This study used Mendelian randomization to identify causal links between plasma proteins and coronary atherosclerosis (AS). Fibronectin 1 emerged as a key therapeutic target for developing new coronary AS treatments.
Area of Science:
- Cardiovascular Research
- Genetics
- Biomarker Discovery
Background:
- Coronary atherosclerosis (AS) is a major cause of cardiovascular disease, posing a significant global health challenge.
- Current therapies for AS face limitations, highlighting the need for novel therapeutic targets.
- Identifying proteins with causal links to AS is crucial for advancing treatment strategies.
Purpose of the Study:
- To identify plasma proteins causally associated with coronary atherosclerosis (AS) using genetic variations.
- To leverage Mendelian randomization analysis for robust identification of potential therapeutic targets.
- To provide a foundation for developing new drugs and therapies for coronary AS.
Main Methods:
- Mendelian randomization analysis was employed using genome-wide association study data for 4907 plasma proteins.
- Inverse variance weighted (IVW) approach was the primary method, supplemented by weighted median, MR-Egger, and mode-based methods for validation.
- Sensitivity analyses, including leave-one-out, were performed to ensure result robustness and exclude biases.
Main Results:
- Twenty potential therapeutic targets were identified with a P-value < .05.
- Fibronectin 1 was highlighted as a key protein target through integrated bioinformatic analyses.
- The study established causal relationships between specific plasma proteins and coronary AS.
Conclusions:
- Fibronectin 1 represents a promising therapeutic target for coronary atherosclerosis.
- This research offers a novel genetic basis for future drug development in cardiovascular disease.
- The findings support the potential for targeted therapies to address limitations in current AS treatment.
Abstract:
Coronary atherosclerosis (AS) is a complicated and severe chronic pathological process that contributes to the basis of various cardiovascular diseases, which causes a serious challenge to the global healthcare system. AS is the underlying physiopathological mechanism. Despite recent advances in the research of biomarkers and therapeutic targets for AS, there remain significant limitations in the current targeted therapies for AS. This study utilizes Mendelian randomization analysis to leverage genetic variations in order to identify plasma proteins with causal relationships to coronary AS. Utilizing publicly available genome-wide association study datasets, 4907 plasma proteins were assessed as exposure factors, with coronary AS being the outcome variable. The primary analytical method employed was the inverse variance weighted approach to ensure the robustness and accuracy of the causal relationships. In addition, to verify the reliability of the results, we employed several complementary methods, including the weighted median, Mendelian randomization-Egger, weighted mode, and simple mode approaches, to thoroughly assess the heterogeneity and pleiotropy of the findings. To ensure the robustness of the results and to exclude potential biases, a leave-one-out sensitivity analysis was performed. Twenty potential therapeutic targets were analyzed and identified (P < .05), combined with multiple bioinformatic analyses; among them, fibronectin 1 was identified as a key target. These findings may provide a new theoretical basis for future research in coronary AS drug development and therapeutic strategies.
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