Early‐life body mass index and the risk of six cardiovascular diseases: A Mendelian Randomization study

Summary Background Observational studies consistently indicate an association between early‐life body mass index (BMI) and several cardiovascular diseases (CVDs). However, the causal relationship remains uncertain. The primary objective of this study was to assess the causal relationship between early‐life BMI and six types of CVDs using the Mendelian Randomization (MR) approach. Methods The dataset for this study was derived from large‐scale, summary‐level Genome‐Wide Association Studies. Specifically, the following datasets we used, early‐life BMI ( n = 61 111, age = 2–10), heart failure (HF) dataset ( n = 977 323), atrial fibrillation (AF) dataset ( n = 1 030 836), coronary artery disease (CAD) dataset ( n = 184 305), peripheral artery disease (PAD) dataset ( n = 243 060), deep venous thrombosis (DVT) dataset ( n = 1 500 861) and myocardial infarction (MI) dataset ( n = 638 000). Multiple MR methods were utilized to evaluate the causal relationship between exposure and outcomes, accompanied by sensitivity analysis. Results Early‐life BMI positively correlates with the risk of developing the six distinct CVDs included in this study. Specifically, elevated BMI during childhood is associated with a 31.9% risk for HF (Odds ratio [OR] = 1.319, 95% CI [1.160 to 1.499], p = 2.33 × 10 −5 ), an 18.3% risk for AF (R = 1.183, 95% CI [1.088 to 1.287], p = 8.22 × 10 −5 ), an 14.8% risk for CAD (OR = 1.148, 95% CI [1.028 to 1.283], p = 1.47 × 10 −2 ), a 40.5% risk for PAD (OR = 1.405, 95% CI [1.233 to 1.600], p = 3.10 × 10 −7 ) and 12.0% risk for MI (OR = 1.120, 95% CI [1.017 to 1.234], p = 2.18 × 10 −2 ). Interestingly, the risk for deep venous thrombosis only increased by 0.5% (OR = 1.005, 95% CI [1.001 to 1.008], p = 2.13 × 10 −3 ). Conclusion Genetically inferred early‐life BMI is significantly associated with six distinct CVDs. This indicates that elevated early‐life BMI is a significant risk factor for multiple cardiovascular disorders.