Jin Xin, Wang Yujue, Zeng Sixuan, Cai Jiarui, Wang Kerui, Ge Qiaoyue, Zhang Lu, Li Xinxi, Zhang Ling, Tong Yu, Luo Xiaoli, Yang Menghan, Zhang Weidong, Yu Chuan, Xiao Chenghan, Liu Zhenmi
Department of Maternal and Child Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
Faculty of Medicine, Imperial College London, London, UK.
Int J Obes (Lond). 2025 Apr;49(4):649-657. doi: 10.1038/s41366-024-01686-1. Epub 2024 Nov 21.
While the association between obesity and kidney diseases has been found in previous studies, the relationship between preschool-age obesity and later-life kidney health remains unclear, posing challenges for effective interventions in this critical life period.
Utilizing the hitherto largest genome-wide association studies, we conducted two-sample mendelian randomization (MR) to estimate the association of preschool age-specific obesity on kidney health and diseases, including blood urea nitrogen (BUN), eGFRcrea, eGFRcys, chronic kidney disease (CKD), IgA nephropathy, and diabetic nephropathy. Then, we applied multivariable Mendelian randomization (MVMR) and stepwise MR to elucidate the role of adult obesity and 12 other potential factors in the pathway between preschool age-specific obesity and kidney health. Finally, we employed colocalization analysis to understand the mechanism of preschool age-specific obesity and kidney damage further by detecting shared causal variants.
Our two-sample MR results indicated that preschool obesity could be associated with kidney health and disease. In addition, we observed a switch in the direction of associations between age-specific body mass index (BMI) and CKD, manifesting as negative associations before 3 years old and positive associations after 3 years old. Furthermore, MVMR and stepwise MR results suggested potential pathways linking preschool obesity to kidney health, involving factors such as adult BMI, circulating high-density lipoprotein cholesterol levels, and circulating C-reactive protein levels. Finally, we detected that preschool-age BMI and kidney function could share causal variants such as rs76111507, rs62107261, rs77165542 in the region of chromosome 2, and rs571312 in the region of chromosome 18.
Our study supports the association between preschool obesity and kidney health, emphasizing the role of adult BMI in this relationship. These findings underscore the importance of interventions starting in early childhood and continuing through adulthood to reduce the long-term risk of obesity-related kidney damage.
虽然先前的研究已发现肥胖与肾脏疾病之间存在关联，但学龄前肥胖与成年后肾脏健康之间的关系仍不明确，这给在这一关键生命阶段进行有效干预带来了挑战。
利用迄今为止最大规模的全基因组关联研究，我们进行了两样本孟德尔随机化（MR）分析，以估计特定学龄前肥胖与肾脏健康及疾病之间的关联，包括血尿素氮（BUN）、基于肌酐的估算肾小球滤过率（eGFRcrea）、基于胱抑素C的估算肾小球滤过率（eGFRcys）、慢性肾脏病（CKD）、IgA肾病和糖尿病肾病。然后，我们应用多变量孟德尔随机化（MVMR）和逐步MR分析，以阐明成人肥胖及其他12个潜在因素在特定学龄前肥胖与肾脏健康之间的通路中的作用。最后，我们采用共定位分析，通过检测共享的因果变异，进一步了解特定学龄前肥胖与肾脏损害之间的机制。
我们的两样本MR分析结果表明，学龄前肥胖可能与肾脏健康及疾病有关。此外，我们观察到特定年龄的体重指数（BMI）与CKD之间的关联方向发生了转变，表现为3岁前呈负相关，3岁后呈正相关。此外，MVMR和逐步MR分析结果提示了将学龄前肥胖与肾脏健康联系起来的潜在通路，涉及成人BMI、循环高密度脂蛋白胆固醇水平和循环C反应蛋白水平等因素。最后，我们检测到学龄前BMI与肾功能可能共享2号染色体区域的rs76111507、rs62107261、rs77165542以及18号染色体区域的rs571312等因果变异。
我们的研究支持学龄前肥胖与肾脏健康之间的关联，强调了成人BMI在这种关系中的作用。这些发现强调了从幼儿期开始并持续至成年期进行干预以降低肥胖相关肾脏损害长期风险的重要性。
