To investigate the causal relationship between four lipid parameters—triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)—and uterine leiomyoma (UL) using a two-sample Mendelian randomization (MR) analysis approach.

Genome-wide association study (GWAS) data for UL and the four lipid parameters were obtained from the IEU open GWAS database. Single nucleotide polymorphisms (SNPs) strongly associated with the lipid parameters were selected as instrumental variables. Two-sample MR analyses were conducted using methods such as inverse variance weighted (IVW) analysis. Subsequently, reverse MR analysis was performed to assess whether there was a reverse causal relationship between the lipid parameters and UL.

The IVW method indicated a negative correlation between TG and the risk of UL (OR=0.996, 95%CI: 0.994-0.998, P<0.001) and a positive correlation between HDL-C and the risk of UL (OR=1.002, 95%CI: 1.000-1.003, P=0.012). No correlation was found between TC or LDL-C and the incidence of UL (P>0.05). Reverse MR analysis did not reveal any reverse causal relationship between the lipid parameters and UL (P>0.05). No horizontal pleiotropy was detected in the above studies (P>0.05).

The level of TG in the body is negatively correlated with the incidence of UL, while the level of HDL-C is positively correlated with the incidence of UL. There is no reverse causal relationship between the four lipid parameters and UL.