#207 : Mendelian Randomization Study Reveals a Casual Effect of Blood Lipids and Apolipoprotein on Uterine Fibroids

Abstract

Background and Aims: Despite an early insight into the risk factors of uterine fibroids (UFs), there is still controversy about the roles of blood lipids and apolipoprotein on UFs. Therefore, to provide more reliable evidence, we investigated the causal effect of blood lipids and apolipoprotein on the risk of UFs through Mendelian randomization (MR). Method: We utilized the large genome-wide association studies of blood lipids and apolipoprotein as instruments and integrated them in the inverse-variance-weighted (IVW) model in two-sample MR to investigate their causal relationship in large sample sizes. To eliminate potential pleiotropy, we listed a conclusive table of genes related to confounding factors, such as body mass index, waist circumference, blood pressure, glucose, hypertension, the metabolic syndrome and smoking and removed the repeated SNPs in the exposure data.To adjust for multiple comparisons, the statistical significance of the MR effect estimates was evaluated in a false discovery rate correlation of less than 5%. Neither pleiotropy nor heterogeneity was reported in all MR sensitivity analysis, including IVW, MR-Egger, simple median, weighted median, weighted mode and Mendelian Randomization Pleiotropy Residual Sum and Outlier methods. Results: Total triglycerides, very low-density lipoprotein (VLDL) cholesterol, including large, medium and small VLDL particles and free cholesterol in large VLDL cholesterol showed positive association with UFs. Meanwhile, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1, free cholesterol in small and medium VLDL and total cholesterol are not statistically related to the development of UFs. Conclusion: Exposure to various aberrant blood lipids increases the risk of UFs, providing genetic evidence for the vital role of aberrant lipid levels in the pathogenesis of UFs. Meanwhile, our results provided genetic insights suggesting intervention in blood lipids might be a prospective strategy in the early prevention and treatment of UFs.