Genetically Determined Reproductive Aging and Coronary Heart Disease: A Bidirectional 2-sample Mendelian...

Area of Science:

• Reproductive Endocrinology
• Cardiovascular Epidemiology
• Genetic Epidemiology

Background:

• Observational studies suggest early menopause increases coronary heart disease (CHD) risk, but the causal direction is unclear.
• An adverse CHD risk profile has been hypothesized to accelerate menopause onset.

Purpose of the Study:

• To investigate the causal relationship between reproductive aging and CHD risk using a bidirectional Mendelian randomization (MR) approach.
• To examine the association of genetically determined age at natural menopause (ANM) with CHD and its risk factors in women and men.

Main Methods:

• Employed a two-sample Mendelian randomization (MR) design.
• Utilized cohort data (EPIC-CVD) and summary statistics (UK Biobank, public GWAS).
• Applied four MR methods: median-based, inverse-variance weighted (IVW), and MR-Egger regression.

Main Results:

• No significant association was found between genetically determined reproductive aging (ANM variants) and CHD risk in women.
• No associations were observed between ANM variants and CHD risk factors in women or men.
• The reverse analysis, examining CHD (risk factors) and reproductive aging, also yielded no significant evidence of a causal link.

Conclusions:

• Genetically determined reproductive aging is not causally linked to CHD risk or risk factors in women.
• No causal association was detected between reproductive aging and CHD in men.
• The study found no evidence for a reverse causal association between CHD (risk factors) and reproductive aging in a combined sample.