Genetics
Mendelian randomisation finds genetically proxied CETP inhibition associated with lower uterine fibroid risk (Heliyon 2025)
Original title: Genetic association of lipid and lipid-lowing drug targets with uterine fibroids
A Mendelian randomisation study tested whether genetically predicted lipid levels and lipid-lowering drug targets causally affect uterine fibroid (UF) risk, using genetic variants from lipid-trait GWAS and drug-target genes against two independent UF GWAS outcomes. HDL-C was protective for UF (odds ratio 0.88, 95% CI, 0.83 to 0.93, P = 3.58E-6) and triglycerides a risk factor (odds ratio 1.14, 95% CI, 1.07 to 1.21, P = 6.83E-5). Drug-target Mendelian randomisation found genetically predicted CETP inhibition associated with lower UF risk (odds ratio 0.95, 95% CI, 0.92 to 0.98, P = 7.83E-4), alongside reduced levels or risk of other UF-associated traits including estradiol, excessive menstruation, abdominal and pelvic pain, myomectomy and miscarriage. A genetic-proxy signal in a condition well outside cardiovascular medicine, the authors call for further investigation rather than claiming a proven drug effect.
Original abstract
Objective: Observational studies suggest that blood lipids are a risk factor for uterine fibroids (UFs) and that lipid-lowering drugs are beneficial for the treatment and prevention of UF; however, the conclusions are inconsistent. We aimed to determine the causal effects of lipids and lipid-lowering drugs on UFs using Mendelian randomization (MR).
Methods: Genetic variants from genome-wide association studies (GWAS) of lipid traits and variants in genes encoding lipid-lowering drug targets were extracted, and two independent UF GWAS were set as the outcome. Their effects on UF risk and related traits were estimated using the inverse variance weighted method.
Results: The MR analysis revealed that high density lipoprotein cholesterol (HDL-C, OR = 0.88, 95 % CI: 0.83-0.93, P = 3.58E-6) and triglycerides (TG, OR = 1.14, 95 % CI: 1.07-1.21, P = 6.83E-5) were protective factors and risk factors for UF, respectively. Drug-targeted MR analysis results indicated that genetically predicted inhibition of cholesteryl ester transfer protein (CETP) was associated with a lower UF risk (OR = 0.95, 95 % CI: 0.92-0.98, P = 7.83E-4), as well as reduced levels or risk of other UF-associated clinical traits, including estradiol level, excessive menstruation, abdominal and pelvic pain, myomectomy, and miscarriage.
Conclusions: Our study provides evidence that HDL-C and TG levels were causally associated with UF risk. Genetically proxied CETP inhibition may have a protective effect against UF, which warrants further investigation.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.