Revealing the Causal Relationship Between Differential White Blood Cell Counts and Depression: A Bidirectional Two-Sample Mendelian Randomization Study

IF 3.3 2区医学 Q1 PSYCHIATRY Depression and Anxiety Pub Date : 2025-03-03 DOI:10.1155/da/3131579

Ying Cao, Xuguang Li, Jing Gao, Nan Zhang, Guoqian Zhang, Shen Li

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Abstract

Background: The link between white blood cells (WBC) and depression has been studied, but the causal relationship remains unclear. This study aimed to elucidate the potential bidirectional causal links between six specific WBC count features and depression using a two-sample Mendelian randomization (MR) analysis, leveraging summary statistics from genome-wide association studies (GWAS).

Method: The dataset on depression (N = 406,986) was sourced from the FinnGen database, while the dataset on WBC (N = 563,085) was obtained from a combined dataset of Blood Cell Consortium (BCX) and UK Biobank. The MR analyses employed include inverse variance weighted (IVW), MR-Egger, weighted median, contamination mixture method (conmix), and constrained maximum likelihood-based Mendelian randomization (cML-MA). A threshold p < 0.05 after false discovery rate (FDR) correction was set as the criterion for causality based on IVW.

Results: Reverse MR analysis indicated a causal relationship where depression leads to an increase in overall WBC count (IVW beta = 0.031, p = 0.015, p_FDR = 0.044) and specifically in basophil count (IVW beta = 0.038, p = 0.006, p_FDR = 0.038), with a marginally significant impact on lymphocyte count (beta = 0.029, p = 0.036, p_FDR = 0.071). Furthermore, forward MR analysis suggested a potential role of monocyte count in decreasing depression risk (p = 0.028), though this association did not retain statistical significance after FDR correction.

Conclusion: These findings suggest that depression may causally influence the immune system by elevating overall WBC and basophil counts, with a marginally significant increase in lymphocyte levels. Conversely, higher monocyte count might confer some protection against depression, albeit with less statistial certainty. This study provides novel insights into the complex interplay between depression and immune function.

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揭示白细胞计数差异与抑郁之间的因果关系：一项双向双样本孟德尔随机研究

背景：白细胞（WBC）与抑郁症之间的联系已被研究，但因果关系尚不清楚。本研究旨在利用全基因组关联研究（GWAS）的汇总统计数据，利用双样本孟德尔随机化（MR）分析，阐明六个特定白细胞计数特征与抑郁症之间潜在的双向因果关系。方法：抑郁症数据集（N = 406,986）来自FinnGen数据库，白细胞数据集（N = 563,085）来自Blood Cell Consortium （BCX）和UK Biobank的联合数据集。采用的磁共振分析包括逆方差加权（IVW）、MR- egger、加权中位数、污染混合法（conmix）和基于约束最大似然的孟德尔随机化（cML-MA）。阈值p <；基于IVW将错误发现率（FDR）校正后的0.05作为因果关系标准。结果：反向MR分析显示，抑郁症导致总白细胞计数（IVW β = 0.031, p = 0.015, pFDR = 0.044），特别是嗜碱性粒细胞计数（IVW β = 0.038, p = 0.006, pFDR = 0.038）增加，对淋巴细胞计数（β = 0.029, p = 0.036, pFDR = 0.071）有轻微显著影响。此外，前向磁共振分析显示单核细胞计数在降低抑郁风险中的潜在作用（p = 0.028），尽管这种关联在FDR校正后没有保持统计学意义。结论：这些研究结果表明，抑郁症可能通过提高白细胞和嗜碱性粒细胞的总计数来影响免疫系统，而淋巴细胞的水平则有轻微的显著增加。相反，较高的单核细胞计数可能对抑郁症有一定的保护作用，尽管在统计上不太确定。这项研究为抑郁症和免疫功能之间复杂的相互作用提供了新的见解。

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来源期刊

Depression and Anxiety 医学-精神病学

CiteScore

15.00

自引率

1.40%

发文量

审稿时长

4-8 weeks

期刊介绍： Depression and Anxiety is a scientific journal that focuses on the study of mood and anxiety disorders, as well as related phenomena in humans. The journal is dedicated to publishing high-quality research and review articles that contribute to the understanding and treatment of these conditions. The journal places a particular emphasis on articles that contribute to the clinical evaluation and care of individuals affected by mood and anxiety disorders. It prioritizes the publication of treatment-related research and review papers, as well as those that present novel findings that can directly impact clinical practice. The journal's goal is to advance the field by disseminating knowledge that can lead to better diagnosis, treatment, and management of these disorders, ultimately improving the quality of life for those who suffer from them.