Table_1_Circulating metabolites and depression: a bidirectional Mendelian randomization.XLSX

BackgroundStudies have shown an association between depression and circulating metabolites, but the causal relationship between them has not been elucidated. The purpose of this study was to elucidate the causal relationship between circulating metabolites and depression and to explore the role of circulating metabolites in depression.
MethodsIn this study, the top single-nucleotide polymorphisms (SNPs) associated with circulating metabolites (n = 24,925) and depression (n = 322,580) were obtained based on the publicly available genome-wide association study using two-sample Mendelian randomization (MR). SNP estimates were summarized through inverse variance weighted, MR Egger, weighted median, MR pleiotropy residual sum and outlier, and “leave-one-out” methods.
ResultsApolipoprotein A-I (OR 0.990, 95% CI 981–0.999) and glutamine (OR 0.985, 95% CI 0.972–0.997) had protective causal effects on depression, whereas acetoacetate (OR 1.021, 95% CI 1.009–1.034), glycoproteins (OR 1.005, 95% CI 1.000–1.009), isoleucine (OR 1.013, 95% CI 1.002–1.024), and urea (OR 1.020, 95% CI 1.000–1.039) had an anti-protective effect on depression. Reversed MR showed no effect of depression on the seven circulating metabolites.
ConclusionIn this study, MR analysis showed that apolipoprotein A-I and glutamine had a protective effect on depression, and acetoacetate, glycoprotein, isoleucine, glucose, and urea may be risk factors for depression. Therefore, further research must be conducted to translate the findings into practice.

背景：已有研究表明抑郁症与循环代谢物存在关联，但二者间的因果关系尚未阐明。本研究旨在阐明循环代谢物与抑郁症之间的因果关系，并探讨循环代谢物在抑郁症发生发展中的作用。
方法：本研究基于公开的全基因组关联研究数据，采用双样本孟德尔随机化（two-sample Mendelian randomization, MR）方法，获取了与循环代谢物（n=24925）及抑郁症（n=322580）相关的顶级单核苷酸多态性（single-nucleotide polymorphisms, SNPs）。本研究通过逆方差加权、MR Egger、加权中位数、孟德尔随机化多效性残差和离群值（MR pleiotropy residual sum and outlier）以及“留一法”等方法对单核苷酸多态性效应估计值进行汇总分析。
结果：载脂蛋白A-I（比值比OR=0.990，95%置信区间CI=0.981~0.999）与谷氨酰胺（OR=0.985，95%CI=0.972~0.997）对抑郁症具有保护性因果效应；而乙酰乙酸（OR=1.021，95%CI=1.009~1.034）、糖蛋白（OR=1.005，95%CI=1.000~1.009）、异亮氨酸（OR=1.013，95%CI=1.002~1.024）及尿素（OR=1.020，95%CI=1.000~1.039）对抑郁症则表现为反保护性效应。反向孟德尔随机化分析显示，抑郁症对上述7种循环代谢物均无显著影响。
结论：本研究通过孟德尔随机化分析发现，载脂蛋白A-I与谷氨酰胺对抑郁症具有保护作用，而乙酰乙酸、糖蛋白、异亮氨酸、葡萄糖及尿素可能为抑郁症的危险因素。因此，需开展进一步研究以将本研究发现转化为临床实践应用。