代谢物和代谢比率与精神分裂症的关系:泯灭随机研究。

IF 3.6 3区 医学 Q1 PSYCHIATRY
Yu Huang, Hanxuan Wang, Jiayu Zheng, Na Zhou
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These analyses assessed the causal effects between blood metabolites, metabolic ratios, and schizophrenia. Tests for pleiotropy and heterogeneity were conducted. False Discovery Rate (FDR) correction was applied to account for multiple comparisons and heterogeneity, ensuring the robustness and reliability of our findings. Consistent with previous studies, an FDR threshold of < 0.2 was considered suggestive of a causal relationship, while an FDR of < 0.05 was considered to indicate a significant causal relationship.</p><p><strong>Results: </strong>The final results revealed that a significant causal association was found between the levels of two metabolites and schizophrenia, Alliin (OR = 0.915, 95%CI = 0.879-0.953, P = 1.93 × 10<sup>- 5</sup>, FDR = 0.013) was associated with a decreased risk of schizophrenia, N-actylcitrulline (OR = 1.058, 95%CI = 1.034-1.083, P = 1.4 × 10<sup>- 6</sup>, FDR = 0.002) was associated with increased risk of schizophrenia. 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The inverse variance-weighted (IVW) method was utilized to estimate the causal relationship between exposure and outcome. To provide a more comprehensive evaluation, additional Mendelian Randomization (MR) approaches were employed, including MR-Egger regression, weighted median, simple mode, and weighted mode methods. These analyses assessed the causal effects between blood metabolites, metabolic ratios, and schizophrenia. Tests for pleiotropy and heterogeneity were conducted. False Discovery Rate (FDR) correction was applied to account for multiple comparisons and heterogeneity, ensuring the robustness and reliability of our findings. 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引用次数: 0

摘要

背景:本研究旨在探讨人体血浆代谢物和代谢比率与精神分裂症(SCZ)的因果关系:本研究旨在探讨人类血浆代谢物和代谢比率与精神分裂症(SCZ)的因果关系:我们采用孟德尔随机化(Mendelian Randomization,MR)方法全面分析了两个大规模代谢组学和精神分裂症全基因组关联研究(Genome-Wide Association Study,GWAS)数据集,共纳入1091种代谢物和309种代谢比,包括52017名精神分裂症患者和75889名健康对照。研究采用反方差加权(IVW)法来估计暴露与结果之间的因果关系。为了提供更全面的评估,还采用了其他孟德尔随机化(MR)方法,包括 MR-Egger 回归法、加权中值法、简单模式法和加权模式法。这些分析评估了血液代谢物、代谢比率和精神分裂症之间的因果效应。对多义性和异质性进行了检验。应用错误发现率(FDR)校正来考虑多重比较和异质性,以确保我们研究结果的稳健性和可靠性。与之前的研究一致,我们将 FDR 的阈值设定为 "结果":最终结果显示,两种代谢物的水平与精神分裂症之间存在明显的因果关系,其中阿利宁(OR = 0.915,95%CI = 0.879-0.953,P = 1.93 × 10- 5,FDR = 0.013)与精神分裂症风险降低相关,N-乳酰瓜氨酸(OR = 1.058,95%CI = 1.034-1.083,P = 1.4 × 10- 6,FDR = 0.002)与精神分裂症风险增加相关。当将 FDR 调整为 0.2 时,结果显示 4 种代谢物水平和 2 种代谢物比率与精神分裂症风险降低有提示性因果关系,包括辛酸 2-氨基酯(OR = 0.904,95%CI = 0.847-0.964,P = 0.002,FDR = 0.160)、N-内酰缬氨酸(OR = 0.853,95%CI = 0.775-0.938,P = 0.001,FDR = 0.122)、X - 21310(OR = 0.917,95%CI = 0.866-0.971,P = 0.003,FDR = 0.195)、X - 26111(OR = 0.932,95%CI = 0.890-0.976,P = 0.003,FDR=0.189),花生四烯酸(20:4n6)与油酸酯与疫苗酸酯(18:1)之比(OR=0.945,95%CI=0.914-0.977,P=8.2×10- 4,FDR=0.104),瓜氨酸与鸟氨酸之比(OR=0.924,95%CI=0.881-0.969,P=0.001,FDR = 0.122),而 4 种代谢物水平和 2 种代谢物比率与精神分裂症风险增加呈提示性因果关系,包括 N2、N5-二乙酰鸟氨酸(OR = 1.090,95%CI = 1.031-1.153,P = 0.003,FDR = 0.185)、N - 乙酰基 - 2-氨基辛酸酯(OR = 1.069,95%CI=(1.027-1.114,P = 0.001,FDR = 0.127)、N - 乙酰基 - 2-氨基己二酸酯(OR = 1.081,95%CI = 1.030-1.133,P = 0.001,FDR = 0.128)、X - 13844(OR = 1.110,95%CI = 1.036-1.190,P = 0.003,FDR = 0.196),X - 24556(或 = 1.083,95%CI = 1.036-1.132,P = 4.5 × 10- 4,FDR = 0.098),X - 24736(或 = 1.065,95%CI = 1.028-1.104,P = 5.6 × 10- 4,FDR = 0.098)、N - 乙酰天冬酰胺(OR = 1.048,95%CI = 1.021-1.075,P = 4.5 × 10- 4,FDR = 0.098)、N - 乙酰精氨酸(OR = 1.060,95%CI = 1.028-1.092,P = 1.8 × 10- 4,FDR = 0.083)、半胱氨酸与丙氨酸比值(OR = 1.086,95%CI = 1.036-1.138,P = 6.5 × 10- 4,FDR = 0.101),以及苯甲酸酯与亚油酰-花生四烯酸酰-甘油(18:2 至 20:4)的比率(OR = 1.070,95%CI = 1.025-1.117,P = 0.002,FDR = 0.158):我们的研究结果为确定与精神分裂症有关的诊断生物标志物提供了有价值的见解,并为进一步探索精神分裂症与新陈代谢之间的关联机制提供了初步研究结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Relationship of metabolites and metabolic ratios with schizophrenia: a mendelian randomization study.

Background: This study aims to investigate the causal relationship of human plasma metabolites and metabolic ratios with schizophrenia (SCZ).

Methods: We employed Mendelian Randomization (MR) approach to comprehensively analyze two large-scale metabolomics and schizophrenia Genome-Wide Association Study (GWAS) datasets, incorporating a total of 1091 metabolites and 309 metabolic ratios, with 52017 schizophrenia patients and 75889 healthy controls. The inverse variance-weighted (IVW) method was utilized to estimate the causal relationship between exposure and outcome. To provide a more comprehensive evaluation, additional Mendelian Randomization (MR) approaches were employed, including MR-Egger regression, weighted median, simple mode, and weighted mode methods. These analyses assessed the causal effects between blood metabolites, metabolic ratios, and schizophrenia. Tests for pleiotropy and heterogeneity were conducted. False Discovery Rate (FDR) correction was applied to account for multiple comparisons and heterogeneity, ensuring the robustness and reliability of our findings. Consistent with previous studies, an FDR threshold of < 0.2 was considered suggestive of a causal relationship, while an FDR of < 0.05 was considered to indicate a significant causal relationship.

Results: The final results revealed that a significant causal association was found between the levels of two metabolites and schizophrenia, Alliin (OR = 0.915, 95%CI = 0.879-0.953, P = 1.93 × 10- 5, FDR = 0.013) was associated with a decreased risk of schizophrenia, N-actylcitrulline (OR = 1.058, 95%CI = 1.034-1.083, P = 1.4 × 10- 6, FDR = 0.002) was associated with increased risk of schizophrenia. When adjusting FDR to 0.2, the results showed that 4 metabolite levels and 2 metabolite ratios were suggestively causally associated with a reduced risk of schizophrenia including 2-aminooctanoate (OR = 0.904, 95%CI = 0.847-0.964, P = 0.002, FDR = 0.160), N-lactoylvaline (OR = 0.853, 95%CI = 0.775-0.938, P = 0.001,FDR = 0.122), X - 21310 (OR = 0.917, 95%CI = 0.866-0.971, P = 0.003,FDR = 0.195), X - 26111 (OR = 0.932, 95%CI = 0.890-0.976, P = 0.003,FDR = 0.189), Arachidonate (20:4n6) to oleate to vaccenate (18:1) ratio (OR = 0.945, 95%CI = 0.914-0.977, P = 8.2 × 10- 4, FDR = 0.104), and Citrulline to ornithine ratio (OR = 0.924, 95%CI = 0.881-0.969, P = 0.001, FDR = 0.122), while 4 metabolite levels and 2 metabolite ratios were suggestively causally associated with an increased risk of schizophrenia including N2, N5-diacetylornithine (OR = 1.090, 95%CI = 1.031-1.153, P = 0.003, FDR = 0.185), N - acetyl - 2-aminooctanoate (OR = 1.069, 95%CI=(1.027-1.114, P = 0.001, FDR = 0.127), N - acetyl - 2-aminoadipate (OR = 1.081, 95%CI = 1.030-1.133, P = 0.001, FDR = 0.128), X - 13844 (OR = 1.110, 95%CI = 1.036-1.190, P = 0.003, FDR = 0.196), X - 24556 (OR = 1.083, 95%CI = 1.036-1.132, P = 4.5 × 10- 4, FDR = 0.098), X - 24736 (OR = 1.065, 95%CI = 1.028-1.104, P = 5.6 × 10- 4, FDR = 0.098), N - acetylasparagine (OR = 1.048, 95%CI = 1.021-1.075, P = 4.5 × 10- 4, FDR = 0.098), N - acetylarginine (OR = 1.060, 95%CI = 1.028-1.092, P = 1.8 × 10- 4, FDR = 0.083), Cysteine to alanine ratio (OR = 1.086, 95%CI = 1.036-1.138, P = 6.5 × 10- 4, FDR = 0.101), and Benzoate to linoleoyl - arachidonoyl - glycerol (18:2 to 20:4) ratio (OR = 1.070, 95%CI = 1.025-1.117, P = 0.002, FDR = 0.158).

Conclusion: Our study results provide valuable insights for identifying diagnostic biomarkers related to schizophrenia and offer preliminary research findings for further exploration of the mechanisms linking schizophrenia and metabolism.

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来源期刊
CiteScore
6.60
自引率
2.70%
发文量
43
审稿时长
>12 weeks
期刊介绍: Annals of General Psychiatry considers manuscripts on all aspects of psychiatry, including neuroscience and psychological medicine. Both basic and clinical neuroscience contributions are encouraged. Annals of General Psychiatry emphasizes a biopsychosocial approach to illness and health and strongly supports and follows the principles of evidence-based medicine. As an open access journal, Annals of General Psychiatry facilitates the worldwide distribution of high quality psychiatry and mental health research. The journal considers submissions on a wide range of topics including, but not limited to, psychopharmacology, forensic psychiatry, psychotic disorders, psychiatric genetics, and mood and anxiety disorders.
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