Yang Jun, Kuang Yalan, Yang Xiaoyan, Li Chunyang, Qi Mei, Fu Ping, Zeng Xiaoxi
Department of Mathematics, Med-X Center for Informatics, Sichuan University, Chengdu, China.
West China Biomedical Big Data Center, West China Hospital, Chengdu, China.
Front Endocrinol (Lausanne). 2024 Jan 15;14:1159547. doi: 10.3389/fendo.2023.1159547. eCollection 2023.
To evaluate the causal relationship between childhood body-mass index (BMI) at different ages and adult cardiometabolic traits.
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.
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.
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.
评估不同年龄阶段的儿童体重指数（BMI）与成人心血管代谢特征之间的因果关系。
我们从相应的全基因组关联分析中检索了暴露因素（新生儿、婴儿、幼儿和儿童晚期的标准化BMI）、心血管代谢特征以及潜在混杂因素或中介因素（成人BMI、性激素结合球蛋白、睾酮和初潮年龄）的遗传工具变量。我们进行了单变量和多变量孟德尔随机化（MR）分析，以剖析特定年龄阶段的儿童BMI与成人心血管代谢结局之间的关联。采用优势比来呈现因果关联的方向。
在单变量MR分析中，较高的新生儿BMI与女性2型糖尿病风险降低存在因果关联。儿童晚期BMI与普通人群中女性患糖尿病、冠状动脉疾病（CAD）、心肌梗死（MI）和慢性肾脏病（CKD）的风险增加有关。在这些关联中，仅在调整成人男性BMI和性激素后，儿童晚期BMI与MI之间的关联仍然显著（OR = 1.120，95%CI 1.023 - 1.226，p = 0.014）。此外，在多变量MR分析中，我们发现有证据表明新生儿BMI与男性CAD风险降低（OR = 0.862，95%CI 0.751 - 0.989，p = 0.034）和MI风险降低（OR = 0.864，95%CI 0.752 - 0.991，p = 0.037）存在因果关联。未发现婴儿或幼儿BMI对上述疾病有明显影响。对于连续性心血管代谢特征，除婴儿期外，在所有年龄阶段，较高的BMI与女性空腹血糖水平升高有关。
出生时和儿童晚期的BMI对成人心血管代谢疾病有不同影响，而婴儿期和幼儿期的BMI与这些结局无因果关联。儿童BMI的影响可能受性别差异影响。
