Exploring the impact of childhood obesity on sarcopenia-related traits: A 2-way Mendelian randomization analysis

Childhood obesity has become a major global public health concern. In recent years, sarcopenia, a syndrome characterized by progressive loss of muscle mass, strength, and function, has shown a tendency to develop at an earlier age and may be associated with metabolic abnormalities in childhood. However, it is difficult to clarify the direction of causality between childhood obesity and sarcopenia, and is subject to confounding factors and reverse causality interference. Mendelian randomization (MR), which uses genetic variation as an instrumental variable, can effectively control confounding and infer causality. Bidirectional MR can further explore the bidirectional causal association between exposure and outcome. This study aimed to clarify the causal direction of childhood obesity and sarcopenia-related traits by using bidirectional MR methods. To examine the relationship between childhood obesity and sarcopenia-related traits, the bidirectional 2-sample MR method was used, and the main analysis method was inverse-variance weighted analysis. The study used genome-wide association study data on childhood obesity, appendicular lean mass, hand grip strength, and walking pace (WP) that were taken from public databases. Childhood obesity and WP may have been causally related, according to the forward MR analysis (odds ratio [OR] = 0.982, 95% confidence interval: 0.966-0.998, P < .05). Reverse MR analysis indicated a link between WP and the risk of childhood obesity (OR = 0.215, 95% confidence interval: 0.047-0.976, P < .05), with accelerated WP reducing the likelihood of childhood obesity. The findings of the other MR analyses, however, did not reveal any noteworthy variations. Childhood obesity was a significant causal factor for reduced walking speed (OR = 0.982, P < .05), whereas increased walking speed significantly prevented the development of childhood obesity (OR = 0.215, P < .05). Although walking speed, one of the core indicators of sarcopenia, had a bidirectional causal association with obesity, the combined diagnosis of sarcopenia was not causally related to childhood obesity. Therefore, walking speed can be used as an independent and practical indicator for screening childhood obesity, assessing muscle function, and monitoring the effects of interventions.