Causal Relationship Between Type 2 Diabetes Mellitus and Preeclampsia: A Bidirectional Two-Sample Mendelian...

Area of Science:

• Obstetrics and Gynecology
• Endocrinology
• Genetics
• Epidemiology

Background:

• Observational studies suggest a link between diabetes mellitus and preeclampsia (PE), but lack genetic evidence.
• Genetic predisposition to type 2 diabetes mellitus (T2DM) and its potential causal effect on PE remain underexplored.

Purpose of the Study:

• To investigate the potential causal relationship between T2DM and PE using a two-sample Mendelian randomization (MR) approach.
• To assess the influence of genetically predicted T2DM on PE risk.

Main Methods:

• A two-sample bidirectional MR analysis was performed using large genome-wide association study datasets for T2DM (N=461,920) and PE (N=219,817).
• Inverse variance weighting (IVW) and other methods (MR-Egger, MR-RAPS, weighted median, weighted mode) were employed to assess causality.
• Reverse MR analysis explored the causal effect of PE on T2DM.

Main Results:

• MR analysis indicated a significant causal association between T2DM and PE (OR=1.10, P=0.01).
• Supporting evidence was found with weighted median (OR=1.19, P=0.022) and weighted mode (OR=1.22, P=0.019) methods.
• No significant causal link was detected from PE to T2DM in reverse analysis. No significant horizontal pleiotropy was observed.

Conclusions:

• This MR study provides the first genetic evidence suggesting a causal link from T2DM to PE.
• The reverse association from PE to T2DM was not supported, potentially due to limited genetic instruments.
• Further research with larger datasets and mechanistic studies is recommended to confirm findings and elucidate pathways.