Genetically Predicted Omega-3 Fatty Acids Mediate the Association between SM23-33 Abundance in Stool and Childhood Obesity: A Mendelian Randomization Study.

Author(s): Min Zhang, Jinke Li, Fang Huang and Wenjuan Yan*

Abstract

Background: Childhood obesity may be linked to gut microbiota and omega-3 fatty acids, but the precise relationships remain unclear.

Objective: This study aimed to investigate the relationships between omega-3 fatty acids, the abundance of SM23-33 in stool, and childhood
obesity.

Methods: We performed Linkage Disequilibrium Score Regression (LDSC) to assess the genetic correlations among the abundance of SM23-33 in stool, omega-3 fatty acids, and childhood obesity. Additionally, bidirectional Mendelian Randomization (MR) analyses were conducted to explore the causal connections between SM23-33 abundance in stool and childhood obesity. A two-step MR analysis was used to determine whether omega-3 fatty acids, specifically Docosahexaenoic Acid (DHA), mediated these relationships. All statistical analyses were conducted using R software, adhering to the STROBE-MR checklist for reporting MR studies.

Results: No significant genetic correlation was found among SM23-33 abundance in stool, omega-3 fatty acids, and childhood obesity (rg_p>0.05). However, MR analysis indicated a causal association between SM23-33 abundance in stool and childhood obesity (OR=0.747, 95% CI: 0.584-0.957, P=0.021). There was no strong evidence that genetically predicted childhood obesity affected SM23-33 abundance in stool. The two-step MR analysis suggested that the association between SM23-33 abundance in stool and childhood obesity was mediated by DHA, with a mediation proportion of 3.56% (95% CI: 3.43%, 3.69%).

Conclusion: This study provides evidence supporting a causal relationship between the abundance of SM23-33 in stool and childhood obesity, with a potential mediating effect by Docosahexaenoic Acid (DHA).

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