Opposite causal effects of birthweight on myocardial infarction and atrial fibrillation and the distinct mediating pathways: a Mendelian randomization study
Authors' conclusion
Cardiometabolic factors mainly mediated the association between lower birthweight and MI, while body composition and strength traits mediated the association between higher birthweight and AF. These findings provide novel evidence for the distinct pathogenesis of MI and AF and advocate adopting a life-course approach to improving fetal development and subsequent causal mediators to mitigate the prevalence and burden of cardiovascular diseases.
Study context
- Population
- GWAS summary statistics for birthweight (N = 297,356 own; 210,248 offspring), myocardial infarction (MI) (61,000 cases, 577,000 controls), AF (60,620 cases, 970,216 controls) and 52 candidate mediators
- Comparison
- Genetically determined birthweight and risk of MI and AF
- Outcome
- Causal effects of birthweight on MI and AF, and mediators in their pathways
Methodological detailstwo-step Mendelian randomization (MR), GWAS summary statistics
- Two-step MR
- GWAS summary statistics
Main finding
As reported in the abstract
MI: higher risk per 1-SD lower birthweight
40%
95% CI 1.22–1.60
AF: higher risk per 1-SD higher birthweight
29%
95% CI 1.16–1.44
Further findings
Mediation of birthweight–MI effect
- Cardiometabolic factors (lipids and lipoproteins, glucose and insulin, blood pressure, fatty acids), each mediated proportion of total effect
- 4.09-23.71%
- Body composition and strength traits (appendicular lean mass, height, grip strength) and socioeconomic indicators (education, household income), each mediated proportion
- 8.08 to 16.80%
Mediation of birthweight–AF effect
- Appendicular lean mass, height, waist circumference, childhood obesity and BMI, each mediated proportion of total effect
- 15.03-45.12%
Fetal-specific and maternal-specific birthweight
- Both fetal-specific and maternal-specific birthweight inversely associated with MI; only fetal-specific birthweight positively associated with AF
Psychological well-being and lifestyle factors
- No mediating effect in either association
Original publication
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