Women's reproductive traits and ischemic stroke: a two-sample Mendelian randomization study.

Area of Science:

• Reproductive health
• Cardiovascular epidemiology
• Genetic epidemiology

Background:

• Women's reproductive behaviors are associated with ischemic stroke (IS) risk.
• The causal pathways and mediating factors, such as body mass index (BMI) and educational attainment (EA), remain unclear.

Purpose of the Study:

• To investigate the causal associations between women's reproductive behaviors and IS using Mendelian randomization (MR).
• To explore the mediating roles of BMI and EA in these associations.

Main Methods:

• Univariable and multivariable Mendelian randomization (MR) analyses were performed using large-scale genome-wide association study summary data.
• MR mediation analysis was employed to assess the indirect effects of reproductive behaviors on IS via BMI and EA.
• Sensitivity analyses were conducted to ensure the validity of MR assumptions.

Main Results:

• Earlier age at first birth (AFB) and age at first sexual intercourse (AFS) were causally associated with an increased risk of IS and large-artery atherosclerotic stroke (LAS).
• Specifically, genetically predicted earlier AFB and AFS showed a reduced risk of IS (OR 0.93 and 0.83, respectively).
• BMI mediated the association between AFS and IS/LAS, while EA mediated the association between AFS/AFB and IS/LAS.

Conclusions:

• Women's reproductive behaviors, specifically earlier AFB and AFS, have a causal impact on IS risk.
• BMI and EA are significant mediators in the relationship between reproductive behaviors and IS, offering potential targets for intervention.
• Findings support the development of targeted prevention strategies for IS in women.