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<p>Tumor necrosis factor (TNF) inhibition is under investigation as a therapeutic strategy for Parkinson’s disease (PD) and REM sleep behavior disorder (RBD), yet supporting genetic evidence is limited. We used Summary-data-based Mendelian Randomization (SMR) to test whether expression level of ten TNF-related genes were causally linked to PD risk, PD progression, or RBD risk. We also analyzed associations between common and rare variants in these genes, and performed pathway specific polygenic risk score analysis, with PD. Overall, our findings do not support a genetic link between the TNF signaling and PD or RBD, arguing against this pathway as a genetically validated therapeutic target.</p>

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No evidence for genetic role of the tumor necrosis factor pathway in Parkinson’s disease

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月9日

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  • Morvarid Ghamgosar Shahkhali,
  • Lang Liu,
  • Emma N. Somerville,
  • Alastair J. Noyce,
  • Ziv Gan-Or,
  • Konstantin Senkevich

摘要

Tumor necrosis factor (TNF) inhibition is under investigation as a therapeutic strategy for Parkinson’s disease (PD) and REM sleep behavior disorder (RBD), yet supporting genetic evidence is limited. We used Summary-data-based Mendelian Randomization (SMR) to test whether expression level of ten TNF-related genes were causally linked to PD risk, PD progression, or RBD risk. We also analyzed associations between common and rare variants in these genes, and performed pathway specific polygenic risk score analysis, with PD. Overall, our findings do not support a genetic link between the TNF signaling and PD or RBD, arguing against this pathway as a genetically validated therapeutic target.