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ORIGINAL RESEARCH article

Front. Psychiatry
Sec. Mood Disorders
Volume 15 - 2024 | doi: 10.3389/fpsyt.2024.1424958
This article is part of the Research Topic Molecular Mechanisms in Psychiatry 2023: Depressive Disorders View all 3 articles

Revealing Genetic Causality Between Blood-Based Biomarkers and Major Depression in East Asian Ancestry

Provisionally accepted
Xiaoxiao Mo Xiaoxiao Mo 1,2Chao Wang Chao Wang 1,2Qiuyi Pu Qiuyi Pu 1,2Zhengdong Zhang Zhengdong Zhang 1,2Dongmei Wu Dongmei Wu 1,2*
  • 1 Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, China
  • 2 Department of Environmental Genomics, School of Public Health, Nanjing Medical University, Nanjing, China

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

    Introduction: Major Depression (MD) is a common mental disorder. In East Asian ancestry, the association, causality, and shared genetic basis between blood-based biomarkers and MD remain unclear. Methods: We investigated the relationships between blood-based biomarkers and MD through a cross-sectional study and Mendelian randomization (MR) analysis. Cross-trait analysis and enrichment analyses were used to highlight the shared genetic determinants and biological pathways. We conducted summary data-based MR to identify shared genes, which were then validated using a transcriptome dataset from drug-naï ve patients with MD. Results: In the cross-sectional study, C-Reactive Protein showed the significantly positive correlation with depressive symptoms, while hematocrit, hemoglobin, and uric acid exhibited significantly negative correlations. In MR analysis, basophil count (BASO) and low-density lipoprotein cholesterol (LDLc) had a significant causal effect on MD.The enrichment analysis indicated a significant role of inflammatory cytokines and oxidative stress. The shared genes MFN2, FAM55C, GCC2, and SCAPER were validated, with MFN2 identified as a pleiotropic gene involved in MD, BASO, and LDLc. Discussion: This study highlighted that BASO and LDLc have a causal effect on MD in East Asian ancestry. The pathological mechanisms of MD are related not only to inflammatory cytokines and oxidative stress but also to down regulation of MFN2 expression and mitochondrial dysfunction.

    Keywords: major depression, Mendelian randomization, basophil, Low-density lipoprotein cholesterol, MFN2

    Received: 29 Apr 2024; Accepted: 26 Aug 2024.

    Copyright: © 2024 Mo, Wang, Pu, Zhang and Wu. 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: Dongmei Wu, Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.