Genetically Predicted Childhood Adiposity and Adult Arterial Plaque Burden: New Insights from Genetic Epidemiology

Aims The causal relationship between childhood adiposity and adult arterial plaque burden remains to be established. Methods and results Two-sample Mendelian randomization (MR) was used to examine the associations of genetically predicted childhood body mass index (BMI) with coronary plaque burden (PB), coronary artery calcification (CAC), and carotid plaque (CP). Multivariable MR and mediation analyses were further performed to explore whether adult BMI, lipid traits, hypertension, or type 2 diabetes (T2D) mediated these associations. A genetically predicted 1-standard deviation increase in childhood BMI was associated with higher coronary PB (β = 0.326; 95% CI, 0.142–0.511) and CAC (β = 0.114; 95% CI, 0.032–0.196), but not CP (β = −0.095; 95% CI, −0.264 to 0.073). Multivariable analyses showed that these associations remained significant after adjustment for low-density lipoprotein cholesterol and T2D, but were attenuated after adjustment for adult BMI, high-density lipoprotein cholesterol, triglycerides (TG), or hypertension—each identified as a significant mediator, with TG accounting for the largest mediated proportion (15.6% for PB; 16.2% for CAC). Conclusions This MR study supports a causal role of childhood adiposity in adult coronary PB and CAC, mediated substantially through adult adiposity, dyslipidemia, and hypertension.