Background: Lipid metabolism disorders were observationally associated with chalazion, but the causality of the related circulating metabolites on chalazion remained unknown. Here, we investigated the potential causal relationship between circulating metabolites and chalazion using two-sample Mendelian randomization (MR) analysis.Methods: For the primary analysis, 249 metabolic biomarkers were obtained from the UK Biobank, and 123 circulating metabolites were obtained from the publication by Kuttunen et al. for the secondary analysis. Chalazion summary data were obtained from the FinnGen database. Inverse variance weighted (IVW) is the main MR analysis method, and the MR assumptions were evaluated in sensitivity and colocalization analyses.Results: Two MR analyses results showed that the common metabolite, alanine, exhibited a genetic protective effect against chalazion (primary analysis: odds ratio [OR] = 0.680; 95% confidence interval [CI], 0.507–0.912; p = 0.010; secondary analysis: OR = 0.578; 95% CI, 0.439–0.759; p = 0.00008). The robustness of the findings was supported by heterogeneity and horizontal pleiotropy analysis. Two colocalization analyses showed that alanine did not share a region of genetic variation with chalazion (primary analysis: PPH4 = 1.95%; secondary analysis: PPH4 = 25.3%). Moreover, previous studies have suggested that an increase in the degree of unsaturation is associated with an elevated risk of chalazion (OR = 1.216; 95% CI, 1.055–1.401; p = 0.007), with omega-3 fatty acids (OR = 1.204; 95% CI, 1.054–1.377; p = 0.006) appearing to be the major contributing factor, as opposed to omega-6 fatty acids (OR = 0.850; 95% CI, 0.735–0.982; p = 0.027).Conclusion: This study suggests that alanine and several unsaturated fatty acids are candidate molecules for mechanistic exploration and drug target selection in chalazion.

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循环代谢物与霰粒肿之间的遗传相关性：双样本孟德尔随机化研究

背景：脂质代谢紊乱在观察上与霰粒肿有关，但相关循环代谢物与霰粒肿的因果关系仍不清楚。在这里，我们使用两样本孟德尔随机化 (MR) 分析研究了循环代谢物与霰粒肿之间的潜在因果关系。方法：对于初步分析，从英国生物库获得了 249 种代谢生物标志物，并从出版物中获得了 123 种循环代谢物库图宁等人。以便进行二次分析。霰粒肿摘要数据来自 FinnGen 数据库。反方差加权（IVW）是主要的MR分析方法，并在敏感性和共定位分析中评估MR假设。结果：两次MR分析结果表明，常见代谢物丙氨酸对霰粒肿表现出遗传保护作用（初步分析：比值比 [OR] = 0.680；95% 置信区间 [CI]，0.507–0.912；p= 0.010；二次分析：OR = 0.578； 95% CI，0.439–0.759；p= 0.00008)。研究结果的稳健性得到了异质性和水平多效性分析的支持。两次共定位分析表明丙氨酸与霰粒肿不共享遗传变异区域（初步分析：PPH4= 1.95%；二次分析：PPH4= 25.3%）。此外，之前的研究表明，不饱和度的增加与霰粒肿风险升高相关（OR = 1.216；95% CI，1.055–1.401；p= 0.007），含有 omega-3 脂肪酸（OR = 1.204；95% CI，1.054–1.377；p= 0.006）似乎是主要影响因素，而不是 omega-6 脂肪酸（OR = 0.850；95% CI，0.735–0.982；p= 0.027）。结论：本研究表明丙氨酸和几种不饱和脂肪酸是霰粒肿机制探索和药物靶点选择的候选分子。