East Asian Mendelian-Randomization Evidence Linking PCOS to Gestational Diabetes Mellitus.

Area of Science:

• Reproductive genetics
• Maternal-fetal medicine
• Epidemiology

Background:

• Previous Mendelian randomization (MR) studies on polycystic ovary syndrome (PCOS) and pregnancy complications were primarily conducted in European populations, limiting generalizability.
• This study addresses the need for research in diverse populations by utilizing East Asian genetic data.

Purpose of the Study:

• To investigate the potential causal relationship between genetically predicted PCOS and adverse pregnancy outcomes in East Asian populations.
• To assess the generalizability of previous findings and explore population-specific genetic influences.

Main Methods:

• A two-sample Mendelian randomization (MR) study design was employed.
• Genetic instruments for PCOS were identified from genome-wide association studies (GWAS) in East Asian populations.
• Outcomes analyzed included gestational diabetes mellitus (GDM), preeclampsia, intrahepatic cholestasis of pregnancy, miscarriage, preterm birth, and gestational age at birth, using inverse variance-weighted (IVW) and multivariable MR (MVMR) methods.

Main Results:

• Genetically predicted PCOS showed a causal association with an increased risk of GDM (OR=1.203).
• This association remained consistent across various sensitivity analyses.
• No significant causal relationships were found between PCOS and other analyzed pregnancy complications.
• MVMR indicated that the PCOS-GDM association was independent of BMI but not of glucose and lipid traits.

Conclusions:

• This MR study provides evidence for a causal link between genetically predicted PCOS and GDM in East Asian populations.
• Findings suggest potential population-specific genetic differences influencing PCOS and pregnancy outcomes.
• Results have implications for precision risk assessment in pregnant individuals with PCOS.