摘要

目的：精神分裂症、重度抑郁症、双相情感障碍的潜在病因仍未被完全了解，最近有研究表明嘌呤代谢途径的代谢物与精神分裂症、重度抑郁症、双相情感障碍之间有关联，但它们之间的因果关系尚不清楚。本研究的
目的是基于双向双样本孟德尔随机化研究探索明嘌呤代谢途径的代谢物与精神分裂症重度抑郁症、双相情感障碍之间的因果关系。

方法：本研究基于欧洲人群中明嘌呤代谢途径的代谢物与精神分裂症重度抑郁症、双相情感障碍的全基因组关联研究（GWAS）的汇总数据。使用双向双样本MR，遗传因素作为工具变量，评估明嘌呤代谢途径的代谢物与精神分裂症重度抑郁症、双相情感障碍的潜在因果关系。

结果：次黄嘌呤与精神分裂症之间有潜在的因果关系，且为负相关，比值比（OR）为0.233（95%CI：0.076-0.719，P = 0.011）. 肌苷与重度抑郁症之间有潜在的因果关系，且为负相关，OR为0.919（95%CI：0.859-0.982，P = 0.013）。硫酸盐与重度抑郁症之间存在潜在的因果关系，OR为1.121（95%CI：1.024-1.227，P = 0.013，）.

结论：本文采用双向双样本孟德尔随机化分析旨在深入探究嘌呤代谢途径与精神分裂症、重度抑郁症、双相情感障碍之间的因果关系。研究

结果表明，次黄嘌呤与精神分裂症之间有潜在的因果关系，且为负相关。肌苷与重度抑郁症之间有潜在的因果关系，且为负相关，硫酸盐与重度抑郁症之间存在潜在的因果关系。这一发现为理解这些精神疾病的发病机制提供了新的视角，揭示了嘌呤代谢途径在精神疾病发生发展中的潜在作用，这些关联仍需要进一步研究。

关键词：嘌呤代谢途径、精神分裂症、双相情感障碍、重度抑郁症、孟德尔随机化

ABSTRACT

Objective: The potential causes of schizophrenia, severe depression, and bipolar disorder are still not fully understood. Recent studies have shown that metabolites of the purine metabolism pathway are associated with schizophrenia, severe depression, and bipolar disorder, but the causal relationship between them is still unclear. The purpose of this study is to explore the causal relationship between metabolites of the purine metabolism pathway and severe depression and bipolar disorder in schizophrenia based on a bidirectional two sample Mendelian randomization study. Method: This study is based on the summary data of the genome-wide association study (GWAS) between metabolites of the purine metabolism pathway and schizophrenia, severe depression, and bipolar disorder in the European population. Using bidirectional dual sample MR and genetic factors as instrumental variables, evaluate the potential causal relationship between metabolites of the purine metabolism pathway and severe depression and bipolar disorder in schizophrenia. Result: There is a potential causal relationship between hypoxanthine and schizophrenia, and it is negatively correlated with an odds ratio (OR) of 0.233 (95% CI: 0.076-0.719, P=0.011) There is a potential causal relationship between inosine and severe depressive disorder, and it is negatively correlated with an OR of 0.919 (95% CI: 0.859-0.982, P=0.013). There is a potential causal relationship between sulfamethoxazole and severe depressive disorder, with an OR of 1.121 (95% CI: 1.024-1.227, P=0.013)

Conclusion  : This article uses bidirectional double sample Mendelian randomization analysis to explore the causal relationship between purine metabolism pathway and schizophrenia, major depression, and bipolar disorder. The research results indicate a potential causal relationship between hypoxanthine and schizophrenia, and it is negatively correlated. There is a potential causal relationship between inosine and severe depression, and it is negatively correlated. There is a potential causal relationship between sulfate and severe depression. This discovery provides a new perspective for understanding the pathogenesis of these mental illnesses, revealing the potential role of purine metabolism pathways in the occurrence and development of mental illnesses, and these associations still require further research.

Key words: purine metabolism pathway, schizophrenia, bipolar disorder, major depression, Mendelian randomization