Novel therapeutic targets for major depressive disorder related to oxidative stress identified by integrative multi-omics and multi-trait study.

IF 5.8 1区医学 Q1 PSYCHIATRY Translational Psychiatry Pub Date : 2024-10-19 DOI:10.1038/s41398-024-03126-0

Xiaojun Shao, Yuan Wang, Zhongli Geng, Guangming Liang, Xiaotong Zhu, Lu Liu, Ming Meng, Li Duan, Gang Zhu

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Abstract

Oxidative stress (OS) is strongly implicated in the pathophysiology of major depressive disorder (MDD) but the molecular mechanisms remain largely unknown. The purpose of this study is to identify genes related to both OS and MDD, and further to evaluate the utility of these genes as diagnostic markers and potential treatment targets. We searched datasets related to MDD from the Gene Expression Omnibus (GEO) database for differentially expressed genes (DEGs) also related to OS according to GeneCards. Bioinformatics analyses and machine learning algorithms were used to identify hub genes mediating OS-MDD interactions. A summary data-based Mendelian randomization (SMR) approach was employed to identify possible causal genes for MDD from blood tissue eQLT data. These investigations identified 32 genes mediating OS-MDD interactions, while SMR analysis identified KCNE1 (OR = 1.057, 95%CI = 1.013-1.102, P value = 0.010), MAPK3 (OR = 1.023, 95%CI = 1.004-1.043, P value = 0.020), and STIP1 (OR = 0.792, 95%CI = 0.641-0.979, P value = 0.031) as OS-related causal genes for MDD. These genes may thus serve as useful diagnostic markers and potential therapeutic targets.

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通过多组学和多性状综合研究发现与氧化应激有关的重度抑郁症新治疗靶点

氧化应激（OS）与重度抑郁症（MDD）的病理生理学密切相关，但其分子机制在很大程度上仍不为人所知。本研究的目的是找出与 OS 和 MDD 相关的基因，并进一步评估这些基因作为诊断标志物和潜在治疗靶点的效用。我们从基因表达总库（Gene Expression Omnibus，GEO）数据库中搜索了与 MDD 相关的数据集，根据 GeneCards 寻找与 OS 同样相关的差异表达基因（DEGs）。生物信息学分析和机器学习算法用于识别介导 OS-MDD 相互作用的枢纽基因。采用基于数据摘要的孟德尔随机化（SMR）方法，从血液组织eQLT数据中找出可能与MDD相关的因果基因。这些研究发现了32个介导OS-MDD相互作用的基因，而SMR分析发现KCNE1（OR = 1.057，95%CI = 1.013-1.102，P值 = 0.010）、MAPK3（OR = 1.023，95%CI = 1.004-1.043，P值 = 0.020）和STIP1（OR = 0.792，95%CI = 0.641-0.979，P值 = 0.031）是与OS相关的MDD致病基因。因此，这些基因可作为有用的诊断标记和潜在的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Psychiatry PSYCHIATRY-

CiteScore

11.50

自引率

2.90%

发文量

484

审稿时长

23 weeks

期刊介绍： Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.