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<p>This investigation elucidates the genetic connection between major depressive disorder (MDD) and metabolic syndrome (MetS), suggesting bidirectional genetic correlations and shared pleiotropic genes. Leveraging a comprehensive genome-wide association study (GWAS) dataset from European and East Asian populations, we discovered new genetic markers linked to MDD and enhanced the robustness of genetic associations via cross-trait analysis. Moreover, the study harnessed computational strategies for drug repurposing, identifying Cytochrome P450 and HDAC inhibitors as candidate drugs for further investigation in MDD and MetS. Employing BLISS technology, we pinpointed proteins significantly linked to both conditions, advancing our comprehension of their molecular underpinnings. Through Mendelian randomization, we investigated how diverse dietary patterns across populations influence MDD and MetS, shedding light on the relationship between diet and disease susceptibility. This research not only enriches our understanding of the intersecting biological pathways of MDD and MetS but also opens avenues for innovative preventive and therapeutic measures.</p>

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Unraveling the genetic interplay and therapeutic potentials between major depressive disorder and metabolic syndrome: multi-ancestry and multi-trait genome-wide association analyses

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月19日

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  • Yiheng Feng,
  • Yihao Li,
  • Hong Zhang,
  • Huilin Xia,
  • Yuan Lu,
  • Hang Zhou,
  • Peng Huang

摘要

This investigation elucidates the genetic connection between major depressive disorder (MDD) and metabolic syndrome (MetS), suggesting bidirectional genetic correlations and shared pleiotropic genes. Leveraging a comprehensive genome-wide association study (GWAS) dataset from European and East Asian populations, we discovered new genetic markers linked to MDD and enhanced the robustness of genetic associations via cross-trait analysis. Moreover, the study harnessed computational strategies for drug repurposing, identifying Cytochrome P450 and HDAC inhibitors as candidate drugs for further investigation in MDD and MetS. Employing BLISS technology, we pinpointed proteins significantly linked to both conditions, advancing our comprehension of their molecular underpinnings. Through Mendelian randomization, we investigated how diverse dietary patterns across populations influence MDD and MetS, shedding light on the relationship between diet and disease susceptibility. This research not only enriches our understanding of the intersecting biological pathways of MDD and MetS but also opens avenues for innovative preventive and therapeutic measures.