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May 14, 2026Journal of Cellular and Molecular Medicine0 citationsOpen Access

Single‐Cell Transcriptome‐Wide Mendelian Randomization and Colocalization Uncover Potential Immunocytes‐Related Therapeutic Targets for Obesity

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XZXingjian ZhangYTYi TianXRXiaoying Ren

Key Points

  • This research aims to identify immune cell-related therapeutic targets linked to obesity through genetic analysis.
  • Conducted single-cell RNA sequencing of blood and adipose tissue samples to identify gene expression changes.
  • Performed Mendelian randomization to assess causal relationships between identified genes and obesity outcomes.
  • Utilized drug-gene interaction databases to find potential drugs targeting specific genes associated with obesity.
  • Identified 41 genes with causal relationships to obesity, including 19 novel genes not previously associated.
  • Specific genes UBE2Z, ZCCHC7, and FNBP4 showed differential expression between lean and obese individuals.
  • Targeted drugs were identified for genes PYGB and PRUNE1, with PYGB being the top-ranked gene for potential therapeutic targeting.

Abstract

naive/central memory T cells and enriched in antigen processing and presentation pathways. Forty-one genes showed causal relationship with all three outcomes, among which 19 genes have not been reported for obesity previously. DEG analysis using single-cell RNA sequencing data of blood or adipose tissue indicated that the differential expression of UBE2Z in monocytes, ZCCHC7 in T cells, and FNBP4 in B cells between lean and obese individuals were consistent with the MR results. By searching drug-gene interaction databases, we found targeted drugs for PYGB and PRUNE1, and PYGB was the top gene ranked in the Tier system. This study provides evidence for the involvement of immune cells in obesity, and the potential cell-specific, immune-related targets for obesity treatment.

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Cite This Study

Zhang et al. (2026) studied this question.

synapsesocial.com/papers/6a0567fda550a87e60a2050ahttps://doi.org/10.1111/jcmm.71185
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