Unraveling the Genetic Interplay and Therapeutic Potentials between Major Depressive Disorder and Metabolic Syndrome: Multi-Ancestry and Multi-Trait Genome-Wide Association Analyses

Abstract

Abstract This investigation elucidates the genetic connection between major depressive disorder (MD) and metabolic syndrome (MetS), uncovering bidirectional interactions 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 MD and enhanced the robustness of genetic associations via cross-trait analysis. Moreover, the study harnessed computational strategies for drug repurposing, highlighting the potential of Cytochrome P450 and HDAC inhibitors as novel treatments for MD 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 MD 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 MD and MetS but also opens avenues for innovative preventive and therapeutic measures.