The impact of age-specific childhood body-mass index on adult cardiometabolic traits: a Mendelian randomization study

Objective To evaluate the causal relationship between childhood body-mass index (BMI) at different ages and adult cardiometabolic traits.Methods We retrieved genetic instrument variables (IVs) for exposures (standardized BMI at newborn, infant, toddler and late childhood), cardiometabolic traits and potential confounders or mediators (adult BMI, SHBG, testosterone and age at menarche) from the corresponding genome-wide association analysis. We performed univariate and multivariable Mendelian randomization (MR) to dissect associations between age-specific childhood BMI and adult cardiometabolic outcomes. Odds ratio was used to present the direction of the causal association.Results In univariate MR, higher newborn BMI was causally associated with reduced risk for type 2 diabetes in women. Late childhood BMI was associated with increased risk for female diabetes and coronary artery disease (CAD), myocardial infarction (MI), and chronic kidney disease (CKD) in general population. Among these associations, only association between late childhood BMI with MI remained significant after adjusting for adult male BMI and sex hormones, (OR = 1.120, 95% CI 1.023-1.226, p = 0.014). Besides, in multivariable MR, we found evidence for causal association between newborn BMI with reduced risk for CAD (OR = 0.862, 95% CI 0.751-0.989, p = 0.034) and MI (OR = 0.864, 95% CI 0.752-0.991, p = 0.037) in men. No obvious impact of infant or toddler BMI was identified on the above-mentioned diseases. For continuous cardiometabolic traits, in all age epochs except infant, higher BMI was associated with increased level of fasting glucose in women.Conclusion BMI at birth and late childhood exerts different impact on adult cardiometabolic diseases, while BMI at infant and toddler ages is not causally associated with these outcomes. The effect of childhood BMI may be influenced by sex disparities.