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孟德尔随机化分析揭示了抑郁症、抗抑郁药与良性阵发性眩晕之间的因果关系。

Mendelian randomization analysis reveals causal relationship between depression, antidepressants and benign paroxysmal vertigo.

作者信息

Liao Yayun, Zhou Kejian, Guo Zhiyan, Qin Lu, Deng Shan, Yang Hong, Weng Baohui, Pan Liya

机构信息

Department of Neurology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, China.

Department of Rehabilitation, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.

出版信息

Sci Rep. 2025 Jan 4;15(1):837. doi: 10.1038/s41598-024-85047-y.

Abstract

Benign paroxysmal vertigo (BPV) is a common cause of dizziness, and some patients are comorbid with psychiatric disorders such as depression, requiring intervention with antidepressants. However, the causal association between BPV, depression and antidepressants has not been clearly established. We used two-sample bidirectional Mendelian randomization (MR) to analyze the causal association between BPV, depression, and antidepressants. From a Finnish database, 43,280 patients with depression and 329,192 controls, and 106,785 patients with antidepressants and 88,536 controls were selected. Independent single nucleotide polymorphisms (SNPs) for depression and antidepressants were used as instrumental variables (IVs) with genomic significance (p < 5 × 10). Similarly, genome-wide association study (GWAS) data for BPV were selected from a Finnish database consisting of 8280 cases and 359,094 controls. Afterwards, a two-sample MR study was performed using R's Two Sample MR and MR-PRESSO software packages. The multiplicity and heterogeneity of the data, as well as the effect of individual SNPs on the results were investigated. The main statistical analyses were weighted median, weighted mode, MR-Egger and weighted inverse variance weighting (IVW) for random effects. Finally, we identified associations between BPV, antidepressants and depression. Four outliers (rs3773087, rs4619804, rs62099231, rs7192848) were found to be associated with depression. After removing the outliers, the statistics showed no heterogeneity (p > 0.05) and horizontal pleiotropy (p > 0.05). Antidepressants were also found to have a random effect IVW (β = 0.440; p = 9.692 × 10; OR = 1.553; 95% CI 1.278-1.887). The inverse MR random effects IVW results showed a causal association between BPV and antidepressants (β = 0.051; p = 0.045; OR = 1.052; 95% CI 1.001-1.1066). In conclusion, there was a significant causal association between antidepressants and BPV at the genetic level. Clinicians should pay attention to patients with BPV combined with depressive disorders and develop timely interventions.

摘要

良性阵发性眩晕(BPV)是头晕的常见原因,一些患者合并有抑郁症等精神疾病,需要使用抗抑郁药进行干预。然而,BPV、抑郁症和抗抑郁药之间的因果关系尚未明确确立。我们使用两样本双向孟德尔随机化(MR)分析BPV、抑郁症和抗抑郁药之间的因果关系。从芬兰数据库中,选取了43280例抑郁症患者和329192例对照,以及106785例使用抗抑郁药的患者和88536例对照。将抑郁症和抗抑郁药的独立单核苷酸多态性(SNP)用作具有基因组意义(p < 5×10)的工具变量(IV)。同样,从一个由8280例病例和359094例对照组成的芬兰数据库中选取BPV的全基因组关联研究(GWAS)数据。之后,使用R的两样本MR和MR-PRESSO软件包进行两样本MR研究。研究了数据的多重性和异质性,以及单个SNP对结果的影响。主要统计分析采用加权中位数、加权众数、MR-Egger和随机效应的加权逆方差加权(IVW)。最后,我们确定了BPV、抗抑郁药和抑郁症之间的关联。发现四个异常值(rs3773087、rs4619804、rs62099231、rs7192848)与抑郁症有关。去除异常值后,统计结果显示无异质性(p > 0.05)和水平多效性(p > 0.05)。还发现抗抑郁药具有随机效应IVW(β = 0.440;p = 9.692×10;OR = 1.553;95% CI 1.278 - 1.887)。反向MR随机效应IVW结果显示BPV与抗抑郁药之间存在因果关系(β = 0.051;p = 0.045;OR = 1.052;95% CI 1.001 - 1.1066)。总之,在基因水平上,抗抑郁药与BPV之间存在显著的因果关系。临床医生应关注合并抑郁症的BPV患者并及时开展干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69de/11700151/333d55232a18/41598_2024_85047_Fig1_HTML.jpg

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