Integrating genetics and transcriptome analyses identify potential biomarkers and immune interactions in metabolic syndrome-related sarcopenia

作者：Wei Fu, Ning Chang, Han Liang, Rong Xu, Kaikai Yang, Li Xu, Xiaoming Wang · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-07191-x · 被引用次数：3 · 研究领域：Genetic Associations and Epidemiology、Nutrition and Health in Aging、Adipokines, Inflammation, and Metabolic Diseases

BACKGROUND: Increasing evidence has indicated that metabolic syndrome (MetS) exists in a close link with sarcopenia; however, the potential mechanism and biomarkers between them remain uninvestigated. This study leverages integrative genetics and transcriptome to identify potential biomarkers and immune interactions in MetS-related sarcopenia. METHODS: We used genome-wide association studies summary statistics for linkage disequilibrium score regression and MiXeR analyses to explore shared genetic architecture between MetS and sarcopenia-related traits. Causal associations were assessed via Mendelian randomization (MR), causal analysis using the summary effect, and summary data-based MR. Cross-phenotype association analysis identified pleiotropic variants, while transcriptome-wide association study revealed shared pleiotropic genes. Single-cell RNA sequencing mapped gene distribution across immune cells and intercellular communication. A clinical predictive model and MetS animal model validated the pleiotropic genes. RESULTS: LDSC analyses uncovered an aggregate group of 13 pairs demonstrating notable genetic correlations. A significant genetic overlap took place between MetS and sarcopenia-related traits. The causal association of MetS with WP and ALM were found. Furthermore, we determined 79 shared risk novel SNPs and 9 pleiotropic genes. These genes had a strong connection to immune cell infiltration, immune-related markers, and immun-related processes. We demonstrated var...