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Published on: December 5, 2015
Causal relationship between uterine fibroids and cardiovascular disease: A two-sample Mendelian randomization study
Jie Cui1, Yue-Chen Zhao, Li-Zhen She
1Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun, Jilin, China.
Insights
Uterine fibroids (UF) may increase the risk of cardioembolic stroke (CES) but decrease the risk of myocardial infarction (MI). This Mendelian randomization study clarifies the causal link between UF and cardiovascular disease (CVD) risks.
Area of Science:
- Cardiovascular Epidemiology
- Reproductive Endocrinology
- Genetic Epidemiology
Background:
- Uterine fibroids (UF) are common benign tumors in women of reproductive age.
- Previous observational studies suggest a potential link between UF and increased cardiovascular disease (CVD) risk.
- The causal relationship between UF and specific CVD outcomes remains unclear.
Purpose of the Study:
- To investigate the causal association between genetic susceptibility to UF and the risk of developing five major CVDs using a Mendelian randomization approach.
- To differentiate the specific impacts of UF on various cardiovascular conditions, including coronary heart disease, myocardial infarction (MI), atrial fibrillation, heart failure, and cardioembolic stroke (CES).
Main Methods:
- Utilized Mendelian randomization (MR) with summary statistics from large genome-wide association studies.
- Employed linkage disequilibrium score regression to assess genome-wide genetic correlation.
- Performed univariate MR (UVMR) and multivariable MR (MVMR) analyses, including sensitivity analyses to ensure result robustness.
Main Results:
- No significant genetic correlation was found between UF and coronary heart disease, MI, atrial fibrillation, or heart failure.
- UVMR indicated a significant causal association between UF and increased risk of CES (OR=1.113, P=0.019) and a suggestive inverse association with MI (OR=0.943, P=0.015).
- MVMR confirmed these findings, showing UF causally increases CES risk (OR=1.104, P=0.027) and decreases MI risk (OR=0.935, P=0.025) after adjusting for confounders.
Conclusions:
- Uterine fibroids are causally associated with an increased risk of cardioembolic stroke.
- Uterine fibroids appear to have a protective effect against myocardial infarction.
- These findings provide a genetic basis for understanding the complex relationship between UF and CVD, warranting further mechanistic research.
Abstract:
Previous studies have indicated that patients with uterine fibroids (UF) may have an elevated risk of cardiovascular disease (CVD), although the causal relationship between UF and CVD remains unclear. In this Mendelian randomization (MR) study, we aimed to investigate the causal association between genetic susceptibility to UF and the risk of developing CVD. We extracted summary statistics for single nucleotide polymorphisms associated with UF and 5 CVDs from multiple databases for further analysis. First, we used linkage disequilibrium score regression to assess the genetic correlation across the genome. Next, we performed univariate MR (UVMR), and to ensure the robustness of our results, we conducted sensitivity analyses using several methods. Additionally, we applied multivariable MR (MVMR) to adjust for potential confounders. The linkage disequilibrium score regression results showed that there was no genetic correlation between UF and coronary heart disease, myocardial infarction (MI), atrial fibrillation, heart failure, cardioembolic stroke (CES). The UVMR revealed a significant association between UF and CES (OR = 1.113, 95% confidence interval [CI]: 1.018-1.218, P = .019, PFDR = .047) and a suggestive causal relationship between UF and MI (OR = 0.943, 95% CI: 0.899-0.989, P = .015, PFDR = .075). In the MVMR analysis, after adjusting for a range of potential confounders, the causal relationships between UF and both CES (OR = 1.104, 95% CI = 1.012-1.205, P = .027) and MI (OR = 0.935, 95% CI = 0.882-0.992, P = .025) remained significant. Our study found that UF increase the risk of CES but decrease the risk of MI, providing a theoretical basis for further research into the underlying mechanisms.
