Genetically predicted triglyceride levels and endometriosis risk: Mendelian randomization with exploratory...

Area of Science:

• Genetics
• Reproductive Biology
• Pharmacology

Background:

• Endometriosis (EM) is a complex condition with unclear etiology.
• Triglyceride (TG) levels and lipid metabolism may play a role in EM pathogenesis.
• Identifying genetic links between TG pathways and EM can reveal novel therapeutic targets.

Purpose of the Study:

• To investigate the genetic association between triglyceride levels and endometriosis risk.
• To identify potential lipid-lowering drug targets relevant to endometriosis.
• To explore the regulatory mechanisms involving identified genes in EM.

Main Methods:

• Genome-wide association study (GWAS) data utilized for two-sample Mendelian randomization (MR) analysis.
• Genetic association between predicted TG levels and EM risk estimated.
• Transcriptome analysis and enrichment pathway analysis performed on identified TG-lowering drug target genes.

Main Results:

• Genetically predicted TG levels were significantly associated with increased EM risk (OR = 1.1853, p = 0.0011).
• Seven TG-lowering drug target genes (e.g., SCN3A, BACE1, APOA1) were identified, with SCN3A, BACE1, and APOA1 upregulated in EM patients.
• Identified genes are involved in lipid transport, cell adhesion, and blood vessel development, regulated by PPARA and ESR1.

Conclusions:

• Triglyceride-related pathways and specific lipid-lowering drug targets are genetically associated with endometriosis risk.
• Fibrate-related targets demonstrate broad relevance in genetic analyses for EM.
• These findings highlight potential therapeutic avenues for endometriosis targeting lipid metabolism.