关键词: 儿童肥胖, ω-3多不饱和脂肪酸, ω-6多不饱和脂肪酸, 二十二碳六烯酸, 孟德尔随机化

Abstract: Objective To investigate the causal relationship between ω-3/6 polyunsaturated fatty acids (PUFAs) and childhood obesity using Mendelian randomization (MR), in order to provide new insights for the health management of childhood obesity. Methods Data from genome-wide association studies (GWAS) were utilized, with seven phenotypes, including ω-3/6 PUFAs, as exposure factors and childhood obesity as the outcome factor. Two-sample MR analysis was conducted using five methods: inverse-variance weighted (IVW), MR-Egger regression, simple mode, weighted median, and weighted mode. The primary conclusions were based on the IVW method, while other methods served as references for robustness. Sensitivity analyses, including heterogeneity, horizontal pleiotropy, MR-PRESSO, leave-one-out, and Steiger tests, were also performed. Results ω-3PUFAs (OR=0.82, 95% CI: 0.71 - 0.96, P=0.012), the ratio of ω-3 PUFAs to total fatty acids (OR=0.83, 95%CI: 0.73 - 0.95, P=0.007), and docosahexaenoic acid (DHA) (OR=0.81, 95%CI: 0.69 - 0.95, P=0.011)were negatively associated with childhood obesity. In contrast, the ω-6/ω-3 PUFA ratio showed a positive association with childhood obesity (OR=1.18, 95%CI: 1.04 - 1.34, P=0.013). No significant causal relationships were observed between ω-6 PUFAs, the ratio of ω-6 PUFAs to total fatty acids, linoleic acid, and childhood obesity (P>0.05). In sensitivity analysis, all six datasets, except for linoleic acid, passed all tests, demonstrating the robustness of the results. Conclusions ω-3 PUFAs, the ratio of ω-3 PUFAs to total fatty acids, and DHA are protective factors against childhood obesity, while the ω-6/ω-3 PUFA ratio is a risk factor. Increasing ω-3 PUFA intake or balancing the intake of ω-3 and ω-6 PUFAs in the diet may help reduce the risk of childhood obesity.

Key words: childhood obesity, ω-3 polyunsaturated fatty acids, ω-6 polyunsaturated fatty acids, ocosahexaenoic acid, Mendelian randomization