Bidirectional Causal Relationships Between Obesity and Executive Function in Children and Adolescents: A Genetic Instrumental Variable Analysis

儿童和青少年肥胖与执行功能之间的双向因果关系:一项遗传工具变量分析

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Abstract

This study examines the causal relationship between obesity and executive function (EF)-including cognitive flexibility, inhibitory control, and working memory-using genetic instrumental variable analysis. A bidirectional two-stage least squares (2SLS) analysis was conducted in 406 children and adolescents. EF was measured by standard cognitive tests, and polygenic risk scores were used as genetic instruments, adjusting for key covariates. Higher BMI causally impaired cognitive regulation, significantly affecting perseverative responses (β = -0.25), categories completed (β = 0.21), TMT-A (β = -0.24), and TMT-B (β = -0.37). No causal effect of EF deficits on obesity was observed. Sensitivity analyses confirmed the unidirectional impact of obesity on cognitive flexibility. Obesity causally impairs cognitive flexibility in youth, highlighting the importance of obesity prevention for cognitive health. Genetic findings should be interpreted with caution due to sensitivity to polygenic risk score construction. Further research should explore gene-environment interactions in larger samples.

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