(PTFS08-06-24) Causal Associations of Birth Weight With Cardiovascular Diseases: A Mendelian Randomization Study

Objectives: This study aimed to investigate the causal associations of birth weight with cardiovascular diseases (CVDs).

Methods: A two-sample Mendelian randomization (MR) analysis was performed by using summary-level data from publicly available genome-wide association studies in participants of European ancestry. Single-nucleotide polymorphisms associated with birth weight were extracted from summary-level data of own genetic effect on own birth weight and the summary-level data of own genetic effect on own birth weight after adjusting for the correlated maternal genotype. Causal associations of birth weight with ten CVDs were evaluated primarily through inverse variance weighting with the multiplicative random effect method. Other MR methods, such as MR egger regression, weighted median, weighted mode and MR-PRESSO were carried out as sensitivity analyses.

Results: After adjusting for the correlated maternal genotype, and in combination with the various MR methods, birth weight was significantly associated with decreased risk of coronary artery disease (OR: 0.71, 95% CI: 0.62-0.82, P=2.54×10^-6), and an increased risk of pulmonary embolism (OR: 1.67, 95% CI: 1.21-2.30, P=1.61×10^-3) and venous thromboembolism (OR: 1.45, 95% CI: 1.14-1.84, P=2.26×10^-3). There was only suggestive evidence supporting the positive associations of birth weight with atrial fibrillation and flutter and heart failure, and no significant causal effects of birth weight on aortic aneurysm, deep vein thrombosis, hypertension and ischemic stroke were observed.

Conclusions: Our results supported previous research that showed birth weight has a lifelong impact on cardiovascular health. The underlying biological mechanisms of this impact need to be elucidated in the future.

Funding Sources: This work was supported by grants from CAMS Innovation Fund for Medical Sciences (CIFMS) (No.2022-I2M-C&T-B-040) and the National Clinical Research Center of Cardiovascular Diseases, Shenzhen. Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen (No. NCRCSZ-2023-015).