Integrative Analyses Reveal <i>Tstd1</i> as a Potential Modulator of HDL Cholesterol and Mitochondrial Function in Mice
High-density lipoprotein (HDL) cholesterol levels are closely associated with human health and diseases. To identify genes modulating plasma HDL levels, we integrated HDL measurements and multi-omics data collected from diverse mouse cohorts and combined a list of systems genetics methods, including...
Guardado en:
| Autores principales: | , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/0a6ea68c86db4f21985c5831812a9295 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| Sumario: | High-density lipoprotein (HDL) cholesterol levels are closely associated with human health and diseases. To identify genes modulating plasma HDL levels, we integrated HDL measurements and multi-omics data collected from diverse mouse cohorts and combined a list of systems genetics methods, including quantitative trait loci (QTL) mapping analysis, mediation analysis, transcriptome-wide association analysis (TWAS), and correlation analysis. We confirmed a significant and conserved QTL for plasma HDL on chromosome 1 and identified that <i>Tstd1</i> liver transcript correlates with plasma HDL in several independent mouse cohorts, suggesting <i>Tstd1</i> may be a potential modulator of plasma HDL levels. Correlation analysis using over 70 transcriptomics datasets in humans and mice revealed consistent correlations between <i>Tstd1</i> and genes known to be involved in cholesterol and HDL regulation. Consistent with strong enrichment in gene sets related to cholesterol and lipoproteins in the liver, mouse strains with high <i>Tstd1</i> exhibited higher plasma levels of HDL, total cholesterol and other lipid markers. GeneBridge using large-scale expression datasets identified conserved and positive associations between <i>TSTD1/Tstd1</i> and mitochondrial pathways, as well as cholesterol and lipid pathways in human, mouse and rat. In summary, we identified <i>Tstd1</i> as a new modulator of plasma HDL and mitochondrial function through integrative systems analyses, and proposed a new mechanism of HDL modulation and a potential therapeutic target for relevant diseases. This study highlights the value of such integrative approaches in revealing molecular mechanisms of complex traits or diseases. |
|---|