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ORIGINAL RESEARCH article

Front. Psychiatry
Sec. Psychopathology
Volume 15 - 2024 | doi: 10.3389/fpsyt.2024.1411280
This article is part of the Research Topic Immunity and Inflammation in Neuropsychiatric Disorders View all 6 articles

Causal role of immune cells in bipolar disorder: a Mendelian randomization study

Provisionally accepted
Mengxuan Wang Mengxuan Wang 1Shuo Wang Shuo Wang 1Guoshan Yuan Guoshan Yuan 1Gao M. Zhou Gao M. Zhou 1Xiyan Zhao Xiyan Zhao 2Zhenhan Chu Zhenhan Chu 1Gao Dongmei Gao Dongmei 1*
  • 1 Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
  • 2 China University of Petroleum (East China), Qingdao, China

The final, formatted version of the article will be published soon.

    Background: The understanding of the immunological mechanisms underlying bipolar disorder (BD) has enhanced in recent years due to the extensive use of high-density genetic markers for genotyping and advancements in genome-wide association studies (GWAS). However, studies on the relationship between immune cells and the risk of BD remain limited, necessitating further investigation. Methods: Bidirectional two-sample Mendelian Randomization (MR) analysis was employed to investigate the causal association between immune cell morphologies and bipolar disorder. Immune cell traits were collected from a research cohort in Sardinia, whereas the GWAS summary statistics for BD were obtained from the Psychiatric Genomics Consortium. Sensitivity analyses were conducted, and the combination of MR-Egger and MR-Presso was used to assess horizontal pleiotropy. Cochran’s Q test was employed to evaluate heterogeneity, and the results were adjusted for false discovery rate (FDR). Results: The study identified six immune cell phenotypes significantly associated with BD incidence (P< 0.01). These phenotypes include IgD- CD27- %lymphocyte, CD33br HLA DR+ CD14- AC, CD8 on CD28+ CD45RA+ CD8br, CD33br HLA DR+ AC, CD14 on CD14+ CD16+ monocyte, and HVEM on CD45RA- CD4+. After adjusting the FDR to 0.2, two immune cell phenotypes remained statistically significant: IgD-CD27-% lymphocyte (OR=1.099, 95% CI: 1.051-1.149, P = 3.51E-05, FDR=0.026) and CD33br HLA DR+ CD14-AC (OR=0.981, 95% CI: 0.971-0.991, P = 2.17E-04, FDR=0.079). In the reverse MR analysis, BD significantly impacted the phenotypes of four monocytes (P< 0.01), including CD64 on CD14+ CD16+ monocyte, CD64 on monocyte, CX3CR1 on CD14- CD16-, CD64 on CD14+ CD16- monocyte. However, after applying the FDR correction (FDR < 0.2), no statistically significant results were observed. Conclusions: This MR investigation reveals associations between immune cell phenotypes, bipolar disorder, and genetics, providing novel perspectives on prospective therapeutic targets for bipolar disorder.

    Keywords: Bipolar Disorder1, immune cells2, mendelian randomization study3, causally association4, SNP5

    Received: 02 Apr 2024; Accepted: 30 Jul 2024.

    Copyright: © 2024 Wang, Wang, Yuan, Zhou, Zhao, Chu and Dongmei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Gao Dongmei, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong Province, China

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