Causal association between uterine fibroids and cardiovascular disease: A Mendelian randomization study

Area of Science:

• Genetics and Epidemiology
• Cardiovascular Research
• Women's Health

Background:

• Uterine fibroids (UF) are common benign tumors in women, with observational studies suggesting a link to cardiovascular disease (CVD).
• Confounding factors in observational studies have obscured a clear causal inference between UF and CVD.
• Mendelian randomization (MR) offers a method to investigate potential causal relationships by utilizing genetic variants.

Purpose of the Study:

• To evaluate the causal effect of genetically predicted uterine fibroids (UF) on the risk of developing cardiovascular disease (CVD) subtypes.
• To leverage genetic variants as instrumental variables (IVs) to overcome confounding in the association between UF and CVD.
• To provide robust evidence regarding the etiological relationship between UF and cardiovascular health.

Main Methods:

• A two-sample Mendelian randomization (MR) study design was employed.
• Genetic variants strongly associated with UF were identified from large-scale genome-wide association studies (GWAS) in European ancestry.
• Summary statistics for CVD outcomes (ischemic heart disease, heart failure, venous thromboembolism, stroke) were obtained from independent consortia (FinnGen, EBI).
• Inverse-variance weighted (IVW) method was the primary analysis, with sensitivity analyses including weighted median, MR-Egger, MR-PRESSO, Cochran's Q, MR-Egger intercept, and leave-one-out analyses to assess robustness and pleiotropy.

Main Results:

• Genetically predicted UF did not show a statistically significant causal effect on ischemic heart disease (OR=0.02, P=0.11).
• No causal association was found between genetically predicted UF and heart failure (OR=0.52, P=0.74), venous thromboembolism (OR=1.65, P=0.89), or stroke (OR=0.37, P=0.71).
• Sensitivity analyses confirmed the robustness of these findings, showing no significant heterogeneity or horizontal pleiotropy.

Conclusions:

• This MR study provides no sufficient evidence to support a causal link between uterine fibroids and major cardiovascular diseases.
• The findings contrast with some previous observational studies, suggesting that the observed associations may be due to confounding factors.
• Further research may be needed to elucidate the complex interplay between UF and cardiovascular health, potentially exploring alternative pathways or specific CVD subtypes.