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ORIGINAL RESEARCH article

Front. Psychiatry
Sec. Schizophrenia
Volume 15 - 2024 | doi: 10.3389/fpsyt.2024.1465291

Mendelian Randomization Analysis of Causal and Druggable Circulating Inflammatory Proteins in Schizophrenia

Provisionally accepted
Hongbao Cao Hongbao Cao 1Li Fu Li Fu 2Dong m. Liu Dong m. Liu 3Ancha Baranova Ancha Baranova 1Fuquan Zhang Fuquan Zhang 2*
  • 1 George Mason University, Fairfax, Virginia, United States
  • 2 Nanjing Medical University, Nanjing, China
  • 3 Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China

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

    Background: Schizophrenia (SZ) is a severe mental disorder with complex origins. Observational studies suggested that inflammatory factors may play a role in the pathophysiology of SZ and we aim to investigate the potential genetic connection between them by examining the causal impact of circulating inflammatory proteins on SZ. Methods: We utilized Mendelian randomization (MR) analysis to assess the causal relationship between circulating inflammatory proteins and SZ and the GWAS summary datasets were sourced from public databases. The SZ dataset comprised 74,776 cases and 101,023 controls, while the summary results for 91 plasma proteins in 14,824 participants were obtained through the Olink Target platform. Moreover, to identify and evaluate potential drug targets, we searched the Drug-Gene Interaction Database (DGIdb). Results: The results of the MR study confirmed that nine inflammatory proteins had a causal effect on SZ. Among these proteins, IL1A (OR: 0.93), TNFB (OR: 0.94), TNFSF14 (OR: 0.96), and CD40 (OR: 0.95) exhibited protective effects against SZ. Conversely, CCL23 (OR: 1.04), CCL19 (OR: 1.04), 4EBP1 (OR: 1.06), TWEAK (OR: 1.08), and DNER (OR: 1.10) were associated with an increased risk of SZ. The MR-Egger and weighted median methods also supported the direction of these effects. According to the Gene-Drug analysis, LTA, IL1A, CD40, and 4EBP1 can serve as drug targets. Conclusions: Our study established causal relationships between circulating inflammatory proteins and SZ. It may be beneficial to personalize the treatment of SZ by incorporating inflammation management into the treatment regimen.

    Keywords: Mendelian randomization, Circulating inflammatory proteins, Schizophrenia, Gene-Drug analysis, GWAS

    Received: 16 Jul 2024; Accepted: 09 Oct 2024.

    Copyright: © 2024 Cao, Fu, Liu, Baranova and Zhang. 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: Fuquan Zhang, Nanjing Medical University, Nanjing, 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.