Chain effect of lifecourse reproductive characteristics and body fat and muscle on cardiovascular disease in women: a Mendelian randomization study
Authors' conclusion
Lifecourse reproductive characteristics and fat- and muscle-related traits manifested reciprocal mediating effects on CVD, informing targeted strategies for bridging cardiovascular health inequalities in women.
Study context
- Population
- Women of European descent; GWAS summary statistics of 16 reproductive traits, 16 fat- and muscle-related traits and five cardiovascular disease (CVD) outcomes (coronary artery disease (CAD), myocardial infarction (MI), HF, AF, ischemic stroke)over one million individuals
- Outcome
- Genetically predicted reproductive traits and CVD outcomes
Methodological detailstwo-sample Mendelian randomization (MR), two-step MR framework
- Two-sample MR
- Two-step MR framework
Main finding
As reported in the abstract
- Age at menarche, OR for CAD
- 0.92
- Age at first sexual intercourse (AFS), OR for CAD
- 0.71
- Age at first birth (AFB), OR for CAD
- 0.89
- Hypertensive disorders of pregnancy (HDP), OR for CAD
- 1.21
- Pre-eclampsia, OR for CAD
- 1.34
- Preterm birth (PTB), OR for CAD
- 1.09
- SHBG, OR for CAD
- 0.73
- Bioavailable testosterone (BT), OR for CAD
- 1.17
- Number of stillbirths, OR for ischemic stroke (IS)
- 2.14
- Fat- and muscle-related traits associated with at least one of five CVD outcomes
- 13
Further findings
Mediating pathways (two-step MR)
- Pathways where AFS, AFB, HDP, PE, PTB, SHBG and BT mediated effects of body composition on five CVD outcomes
- 30
- Pathways where WHR, trunk-trunk fat ratio, abdominal subcutaneous and gluteofemoral adipose tissue mediated effects of reproductive traits on CAD and MI
- nine
Original publication
Chain effect of lifecourse reproductive characteristics and body fat and muscle on cardiovascular disease in women: a Mendelian randomization study. Cardiovasc Diabetol. Published 18 April 2025. doi:10.
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