Mendelian randomization study on the effect of tumor necrosis factor on schizophrenia.

IF 1.5 4区医学 Q4 GENETICS & HEREDITY

Psychiatric Genetics Pub Date : 2022-12-01 DOI:10.1097/YPG.0000000000000329

Ning Ma, Renxi Wang

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引用次数: 1

Abstract

Objective: Previous observational studies have shown that the levels of tumor necrosis factor (TNF) increased in patients with schizophrenia. The present two-sample Mendelian randomization (MR) study aims to identify the causal link between TNF and schizophrenia.

Methods: To date, the largest genome-wide association study (GWAS) for TNF (n = 23 141) and for schizophrenia (53 386 cases and 77 258 controls) was used. All participants were of European ancestry. The MR-egger_intercept test and Cochran's Q statistic were used to determine the pleiotropy and heterogeneity, respectively. Weighted median and inverse variance weighted (IVW) were used to evaluate the causal association of TNF with schizophrenia.

Results: We found no significant pleiotropy or heterogeneity of all three selected plasma TNF genetic instrumental variants in breast cancer GWAS. Interestingly, the odds ratio (OR) = 1.517 with 95% confidence interval (CI), 1.006-2.288 and P = 0.047 of schizophrenia correspond to one unit increase in natural log-transformed TNF levels using IVW method. The increased trend was further proven using weighted median (OR = 1.585; 95% CI, 1.017-2.469; P = 0.042). Reverse MR analysis shows no causal effect of schizophrenia on plasma TNF levels.

Conclusions: Our analysis suggested a causal association between genetically increased TNF signaling and increased risk of schizophrenia in the European population. Thus, TNF may be a potential risk for schizophrenia.

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肿瘤坏死因子对精神分裂症影响的孟德尔随机化研究。

目的:以往的观察性研究表明，精神分裂症患者的肿瘤坏死因子(TNF)水平升高。目前的两样本孟德尔随机化(MR)研究旨在确定TNF和精神分裂症之间的因果关系。方法:迄今为止，使用了TNF (n = 23 141)和精神分裂症(53 386例和77 258例对照)的最大全基因组关联研究(GWAS)。所有的参与者都有欧洲血统。采用MR-egger_intercept检验和Cochran’s Q统计量分别确定多效性和异质性。使用加权中位数和反方差加权(IVW)来评估TNF与精神分裂症的因果关系。结果:我们发现乳腺癌GWAS中所有三种选择的血浆TNF遗传工具变异均无显著的多效性或异质性。有趣的是，使用IVW方法，精神分裂症的比值比(OR) = 1.517, 95%置信区间(CI)， 1.006-2.288和P = 0.047对应于自然对数转化TNF水平增加一个单位。使用加权中位数(OR = 1.585;95% ci, 1.017-2.469;p = 0.042)。反向磁共振分析显示，精神分裂症对血浆TNF水平无因果影响。结论:我们的分析表明，在欧洲人群中，遗传增加的TNF信号和增加的精神分裂症风险之间存在因果关系。因此，TNF可能是精神分裂症的潜在风险。

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

Psychiatric Genetics 医学-神经科学

CiteScore

2.30

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： The journal aims to publish papers which bring together clinical observations, psychological and behavioural abnormalities and genetic data. All papers are fully refereed. Psychiatric Genetics is also a forum for reporting new approaches to genetic research in psychiatry and neurology utilizing novel techniques or methodologies. Psychiatric Genetics publishes original Research Reports dealing with inherited factors involved in psychiatric and neurological disorders. This encompasses gene localization and chromosome markers, changes in neuronal gene expression related to psychiatric disease, linkage genetics analyses, family, twin and adoption studies, and genetically based animal models of neuropsychiatric disease. The journal covers areas such as molecular neurobiology and molecular genetics relevant to mental illness. Reviews of the literature and Commentaries in areas of current interest will be considered for publication. Reviews and Commentaries in areas outside psychiatric genetics, but of interest and importance to Psychiatric Genetics, will also be considered. Psychiatric Genetics also publishes Book Reviews, Brief Reports and Conference Reports.