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...

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Autores principales:	Adi Zheng, Hao Li, Zhihui Feng, Jiankang Liu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	integrative analysis HDL quantitative trait loci (QTL) mediation analysis transcriptome-wide association analysis (TWAS) correlation analysis Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0a6ea68c86db4f21985c5831812a9295
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spelling	oai:doaj.org-article:0a6ea68c86db4f21985c5831812a92952021-11-25T17:09:57ZIntegrative Analyses Reveal <i>Tstd1</i> as a Potential Modulator of HDL Cholesterol and Mitochondrial Function in Mice10.3390/cells101129762073-4409https://doaj.org/article/0a6ea68c86db4f21985c5831812a92952021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2976https://doaj.org/toc/2073-4409High-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.Adi ZhengHao LiZhihui FengJiankang LiuMDPI AGarticleintegrative analysisHDLquantitative trait loci (QTL)mediation analysistranscriptome-wide association analysis (TWAS)correlation analysisBiology (General)QH301-705.5ENCells, Vol 10, Iss 2976, p 2976 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	integrative analysis HDL quantitative trait loci (QTL) mediation analysis transcriptome-wide association analysis (TWAS) correlation analysis Biology (General) QH301-705.5
spellingShingle	integrative analysis HDL quantitative trait loci (QTL) mediation analysis transcriptome-wide association analysis (TWAS) correlation analysis Biology (General) QH301-705.5 Adi Zheng Hao Li Zhihui Feng Jiankang Liu Integrative Analyses Reveal <i>Tstd1</i> as a Potential Modulator of HDL Cholesterol and Mitochondrial Function in Mice
description	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.
format	article
author	Adi Zheng Hao Li Zhihui Feng Jiankang Liu
author_facet	Adi Zheng Hao Li Zhihui Feng Jiankang Liu
author_sort	Adi Zheng
title	Integrative Analyses Reveal <i>Tstd1</i> as a Potential Modulator of HDL Cholesterol and Mitochondrial Function in Mice
title_short	Integrative Analyses Reveal <i>Tstd1</i> as a Potential Modulator of HDL Cholesterol and Mitochondrial Function in Mice
title_full	Integrative Analyses Reveal <i>Tstd1</i> as a Potential Modulator of HDL Cholesterol and Mitochondrial Function in Mice
title_fullStr	Integrative Analyses Reveal <i>Tstd1</i> as a Potential Modulator of HDL Cholesterol and Mitochondrial Function in Mice
title_full_unstemmed	Integrative Analyses Reveal <i>Tstd1</i> as a Potential Modulator of HDL Cholesterol and Mitochondrial Function in Mice
title_sort	integrative analyses reveal <i>tstd1</i> as a potential modulator of hdl cholesterol and mitochondrial function in mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0a6ea68c86db4f21985c5831812a9295
work_keys_str_mv	AT adizheng integrativeanalysesrevealitstd1iasapotentialmodulatorofhdlcholesterolandmitochondrialfunctioninmice AT haoli integrativeanalysesrevealitstd1iasapotentialmodulatorofhdlcholesterolandmitochondrialfunctioninmice AT zhihuifeng integrativeanalysesrevealitstd1iasapotentialmodulatorofhdlcholesterolandmitochondrialfunctioninmice AT jiankangliu integrativeanalysesrevealitstd1iasapotentialmodulatorofhdlcholesterolandmitochondrialfunctioninmice
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Integrative Analyses Reveal <i>Tstd1</i> as a Potential Modulator of HDL Cholesterol and Mitochondrial Function in Mice

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