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Updated: May 24, 2025

Author Spotlight: Nuclei Isolation from Mouse Cardiac Progenitor Cells for Epigenome and Gene Expression Profiling at Single-Cell Resolution
Published on: May 12, 2023
Mendelian randomization provides a multi-omics perspective on the regulation of genes involved in ribosome biogenesis
Shuxu Wei1,2, Ronghuai Shen1, Xiaojia Lu1
1Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, No.57, Changping Road, Shantou, 515041, China.
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 suggest a link between RiboSis and cardiac health, enhancing understanding of cardiac disease mechanisms.
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