Preschool age-specific obesity and later-life kidney health: a Mendelian randomization and colocalization study

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.