Abstract
BACKGROUND: The causal relationship between childhood adiposity and adult risk of heart diseases has not been clearly demonstrated. This study aims to ascertain whether genetically predicted childhood body mass index (BMI) and childhood obesity are causally associated with adult coronary heart disease, myocardial infarction, heart failure, atrial fibrillation, hypertrophic cardiomyopathy, and pulmonary heart disease. METHODS AND RESULTS: To investigate the causative relationships and underlying mechanisms between childhood adiposity and adult heart diseases, 3 main methods of Mendelian randomization were used: 2-sample Mendelian randomization, multivariable Mendelian randomization with controlling for several cardiometabolic risk variables, and mediation analysis. Every 1-SD rise in genetically predicted childhood body mass index was associated with 24% (odds ratio [OR], 1.24 [95% CI, 1.12-1.37]), 28% (OR, 1.28 [95% CI, 1.14-1.42]), 28% (OR, 1.28 [95% CI, 1.14-1.42]), and 27% (OR, 1.27 [95% CI, 1.04-1.49]) higher risk of coronary heart disease, myocardial infarction, heart failure, and atrial fibrillation, respectively. Every 1-unit increase in log-odds in childhood obesity was associated with 11% (OR, 1.11 [95% CI, 1.06-1.16]), 14% (OR, 1.14 [95% CI, 1.04-1.23]), 10% (OR, 1.10 [95% CI, 1.03-1.18]), and 20% (OR, 1.20 [95% CI, 1.08-1.32]) higher risk of coronary heart disease, myocardial infarction, heart failure, and atrial fibrillation, respectively. The link between childhood adiposity and adult heart diseases was found to be mediated by high-density lipoprotein cholesterol, triglyceride, hypertension, and type 2 diabetes. CONCLUSIONS: Our findings support the causal relationships between childhood adiposity and risk of adult coronary heart disease, myocardial infarction, heart failure, and atrial fibrillation. Blood lipids, hypertension, and type 2 diabetes are factors that mediate the aforementioned associations.