The Association of Redox Regulatory Drug Target Genes with Psychiatric Disorders: A Mendelian Randomization Study

Lu, Zhe; Yang, Yang; Zhao, Guorui; Zhang, Yuyanan; Sun, Yaoyao; Liao, Yundan; Kang, Zhewei; Feng, Xiaoyang; Sun, Junyuan; Yue, Weihua

doi:10.3390/antiox13040398

Cited by 3 publications

(1 citation statement)

References 56 publications

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“…Impaired antioxidant function and ROS production are potential pathogenic mechanisms in SCZ. Redox-related molecules are altered in SCZ patients [ 33 , 34 ]. DJ-1 is an antioxidant protein that regulates the expression of antioxidant defence genes, protecting cells from oxidative stress damage [ 35 , 36 ].…”

Section: Exosomes In the Diagnosis Of Mind And Volition Disordersmentioning

confidence: 99%

Exosomes in the Diagnosis of Neuropsychiatric Diseases: A Review

Wu,

Shang,

Guo

et al. 2024

Biology

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Exosomes are 30–150 nm small extracellular vesicles (sEVs) which are highly stable and encapsulated by a phospholipid bilayer. Exosomes contain proteins, lipids, RNAs (mRNAs, microRNAs/miRNAs, long non-coding RNAs/lncRNAs), and DNA of their parent cell. In pathological conditions, the composition of exosomes is altered, making exosomes a potential source of biomarkers for disease diagnosis. Exosomes can cross the blood–brain barrier (BBB), which is an advantage for using exosomes in the diagnosis of central nervous system (CNS) diseases. Neuropsychiatric diseases belong to the CNS diseases, and many potential diagnostic markers have been identified for neuropsychiatric diseases. Here, we review the potential diagnostic markers of exosomes in neuropsychiatric diseases and discuss the potential application of exosomal biomarkers in the early and accurate diagnosis of these diseases. Additionally, we outline the limitations and future directions of exosomes in the diagnosis of neuropsychiatric diseases.

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Section: Exosomes In the Diagnosis Of Mind And Volition Disordersmentioning

confidence: 99%

Exosomes in the Diagnosis of Neuropsychiatric Diseases: A Review

Wu,

Shang,

Guo

et al. 2024

Biology

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

Shao,

Wang,

Geng

et al. 2024

Transl Psychiatry

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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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Causal relationship between drug target genes of LDL-cholesterol and coronary artery disease: Drug Target Mendelian Randomization Study

Jee,

Shin,

Ryu

et al. 2024

Preprint

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Background High LDL-cholesterol (LDL-C) is a well-known risk factor for coronary artery disease (CAD). PCSK9, HMGCR, NPC1L1, ACLY, and LDLR gene have been reported as lipid lowering drug genes related to LDL-C lowering. However relevant Asian studies were rare. Methods We examined the causality between LDL-c drug target genes and CAD using Korean and Japanese data using the two sample Mendelian Randomization (MR) method. We conducted two-sample MR analysis of LDL-c lowering drug target genes (7 Single-nucleotide polymorphisms (SNP) in PCSK9, 6 SNPs in HMGCR, 5 SNPs in NPC1L1, 9 SNPs in ACLY, 3 SNPs in LDLR) and CAD. We used summary statistics data from the Korean Genome Epidemiology Study (KOGES) for LDL-C data, and Biobank of Japan (BBJ) for CAD data. Results For every 10 mg/dl decrease in LDL-C determined by four significant SNPs in the PCSK9 gene, the risk of CAD decreased by approximately 20% (OR = 0.80, 95% CI: 0.75–0.86). The risk of CAD decreased by 10% for every 10 mg/dl decrease in LDL-C due to the six significant SNPs in the HMGCR gene (OR = 0.90, 95% CI: 0.86–0.94). Due to the two significant SNPs in the gene LDLR, the risk of CAD decreased by approximately 26% for every 10 mg/dl decrease in LDL-C (OR = 0.74, 95% CI: 0.66–0.82). The combined effect on CAD showed the largest effect size for the PCSK9 gene and LDLR gene, and the reduced CAD risk induced by these two genes together was OR = 0.78 (95%CI, 0.74–0.83). Finally, the combined effect of all three genes (PCSK9, HMGCR, and LDLR) was OR = 0.85 (95%CI, 0.79–0.91) (Fig. 3D). Conclusion LDL-C reduction estimated by SNPs in LDL-C lowering drug target genes significantly reduced the risk of CAD. We found the potential of using of proxy research design for clinical trials using LDL-C lowering drugs.

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The Association of Redox Regulatory Drug Target Genes with Psychiatric Disorders: A Mendelian Randomization Study

Cited by 3 publications

References 56 publications

Exosomes in the Diagnosis of Neuropsychiatric Diseases: A Review

Exosomes in the Diagnosis of Neuropsychiatric Diseases: A Review

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

Causal relationship between drug target genes of LDL-cholesterol and coronary artery disease: Drug Target Mendelian Randomization Study

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