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Background <p>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.</p> Methods <p>We utilized summary stats for methylation, RNA splicing, and gene expression, and UK Biobank cardiopulm MRI genetic associations (<i>N</i> = 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.</p> Results <p>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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月5日

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  • Shuxu Wei,
  • Ronghuai Shen,
  • Xiaojia Lu,
  • Xinyi Li,
  • Lingbin He,
  • Youti Zhang,
  • Jiahang Yang,
  • Zhouwu Shu,
  • Xianxi Huang

摘要

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.