AI Article Synopsis
- In a study assessing the link between inflammation-related proteins and major depressive disorder (MDD), researchers aimed to clarify the causal relationship using genetic data from a large sample size.
- The analysis found significant associations between specific proteins (like CASP-8 and IL-18) and the risk of developing MDD, as well as the reverse relationship where MDD is associated with proteins like CCL19 and HGF.
- Identified proteins such as CD40 and IL-18 might serve as potential therapeutic targets, providing insights into the inflammatory mechanisms behind MDD.
Article Abstract
Background: In numerous observational studies, circulating inflammation-related proteins have been linked with major depressive disorder (MDD), yet the precise causal direction of this relationship remains unclear. This study aims to investigate the potential causal link between inflammation-related proteins and the risk of developing MDD.
Methods: We utilized summary data from a genome-wide association study (GWAS) of 91 circulating inflammation-associated proteins in 14,824 individuals of European descent. Additionally, we incorporated findings from a substantial GWAS on MDD, which included 294,322 cases and 741,438 controls. Our analysis employed a two-sample bidirectional Mendelian randomization (MR) approach, with inverse variance weighting (IVW) as the primary method. We augmented this with two supplementary techniques (MR-Egger and weighted median approaches) to detect and address potential pleiotropy. Furthermore, to identify and evaluate possible drug targets, we conducted a thorough search within the Drug-Gene Interaction Database (DGIdb).
Results: Analysis using MR unveiled significant and causative associations between genetically determined CASP-8 (odds ratio (OR): 0.97), CD40 (OR: 0.96), IL-18 (OR: 0.98), SLAMF1 (OR: 0.97), and uPA (OR: 0.98) with MDD. Conversely, reverse MR analysis indicated causal associations between MDD and CCL19 (OR: 1.15), HGF (OR: 1.15), IL-8 (OR: 1.10), IL-18 (OR: 1.11), IL20RA (OR: 1.12), TGFA (OR: 1.12) and TNFSF14 (OR: 1.16). Notably, a significant bidirectional causal link was observed between IL-18 and MDD. Gene-drug analysis identified CD40, HGF, IL-8, IL-18, SLAMF1, and TGFA as potential therapeutic targets.
Conclusions: We've pinpointed causal links between inflammation-related proteins and MDD, offering compelling and innovative evidence to enhance our understanding of the inflammatory mechanisms involved in MDD and to investigate potential targets for anti-MDD medications.
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| http://dx.doi.org/10.1016/j.pnpbp.2024.111165 | DOI Listing |
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