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

摘要： 目的 运用孟德尔随机化(MR)的方法来探讨ω-3/6多不饱和脂肪酸(PUFA)与儿童肥胖的因果关联,以期为儿童肥胖的健康管理提供新的参考。方法 利用全基因组关联研究(GWAS)的数据,ω-3/6 PUFA等7种表型作为暴露因素,儿童肥胖为结局因素。采用逆方差加权法(IVW)、MR-Egger回归、简单模型、加权中位数、加权模型等5种方法进行两样本MR分析。结论主要参照IVW法,其他分析方法的仅作为结果稳健性的参考。并进行异质性、水平多效性、MR-PRESSO、留一法、Steiger检验等敏感性分析。结果 ω-3 PUFA(OR=0.82, 95%CI:0.71~0.96,P=0.012)、ω-3 PUFA与总脂肪酸比率(OR=0.83, 95%CI: 0.73~0.95, P=0.007)、二十二碳六烯酸(DHA)(OR=0.81, 95%CI: 0.69~0.95, P=0.011)与儿童肥胖呈负相关性,但ω-6/ω-3 PUFA比值与儿童肥胖呈正相关性(OR=1.18,95%CI: 1.04~1.34, P=0.013),未观察到ω-6 PUFA、ω-6 PUFA与总脂肪酸比率、亚油酸(PHA)与儿童肥胖存在显著的因果关联(P＞0.05)。在敏感性分析中,除亚油酸外的其余六组数据均通过了全部检验,表明结果具有良好的稳健性。结论 ω-3 PUFA、ω-3 PUFA与总脂肪酸的比率、DHA是儿童肥胖的保护因素;ω-6/ω-3 PUFA比值是儿童肥胖风险因素。在膳食中增加ω-3 PUFA的含量或平衡ω-3和ω-6 PUFA的摄入量可能有利于降低儿童发生肥胖风险。

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