Mendelian randomization provides a multi-omics perspective on the regulation of genes involved in ribosome biogenesis in relation to cardiac structure and function

作者：Shuxu Wei, Ronghuai Shen, Xiaojia Lu, Xinyi Li, Lingbin He, Youti Zhang, Jiahang Yang, Zhouwu Shu, Xianxi Huang · 发表于：Clinical Epigenetics · 年份：2025 · DOI：10.1186/s13148-025-01850-y · 被引用次数：3 · 研究领域：RNA modifications and cancer、Genetic Associations and Epidemiology、Sirtuins and Resveratrol in Medicine

BACKGROUND: Ribosome biogenesis (RiboSis) is a complex process for generating ribosomes, the cellular machinery responsible for protein synthesis. Dysfunctional RiboSis can disrupt cardiac structure and function, contributing to cardiovascular diseases. This study employed a Mendelian randomization (MR) approach, integrating multi-omics data, to investigate the relationship between RiboSis-related genes and standard cardiac structure and function. METHODS: We utilized summary stats for methylation, RNA splicing, and gene expression, and UK Biobank cardiopulm MRI genetic associations (N = 41,135). MR evaluated RiboSis gene features against traits, complemented by hypothesis prioritization for multi-trait colocalization (HyPrColoc) and colocalization. Composite scores ranked RiboSis genes, and phenome-wide association study (PheWAS) with scQTLbase instrumental variables (IVs) confirmed results. RESULTS: We identified 15 RiboSis-related genes: HEATR1, SENP3, ERI1, ERCC2, TSR1, UTP11, DDX17, SMARCB1, NIP7, ERAL1, NOP56, RPL10A, EIF6, EXOSC9, and NOP58. Notably, HEATR1 and SENP3 were ranked in the top quartile (Q1), scoring 25. In validation cohort, 12 genes associated with cardiac structures, functions, diseases. Only ERAL1, TSR1, and NIP7 lacked significant associations with cardiac traits. CONCLUSION: Our multi-omics MR analysis identified 15 RiboSis-related genes associated with cardiac risk, with 12 further validated through gene set enrichment analysis. These findings sugges...