RNA-seq driven expression and enrichment analysis to investigate CVD genes with associated phenotypes among high-risk heart failure patients

Abstract Background Heart failure (HF) is one of the most common complications of cardiovascular diseases (CVDs) and among the leading causes of death in the US. Many other CVDs can lead to increased mortality as well. Investigating the genetic epidemiology and susceptibility to CVDs is a central fo...

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Autores principales:	Zeeshan Ahmed, Saman Zeeshan, Bruce T. Liang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Cardiovascular Disease Expression Enrichment Gene Heart failure Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/f0149186e0b14a1a9d7c8e309e28bd3d
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spelling	oai:doaj.org-article:f0149186e0b14a1a9d7c8e309e28bd3d2021-11-14T12:15:36ZRNA-seq driven expression and enrichment analysis to investigate CVD genes with associated phenotypes among high-risk heart failure patients10.1186/s40246-021-00367-81479-7364https://doaj.org/article/f0149186e0b14a1a9d7c8e309e28bd3d2021-11-01T00:00:00Zhttps://doi.org/10.1186/s40246-021-00367-8https://doaj.org/toc/1479-7364Abstract Background Heart failure (HF) is one of the most common complications of cardiovascular diseases (CVDs) and among the leading causes of death in the US. Many other CVDs can lead to increased mortality as well. Investigating the genetic epidemiology and susceptibility to CVDs is a central focus of cardiology and biomedical life sciences. Several studies have explored expression of key CVD genes specially in HF, yet new targets and biomarkers for early diagnosis are still missing to support personalized treatment. Lack of gender-specific cardiac biomarker thresholds in men and women may be the reason for CVD underdiagnosis in women, and potentially increased morbidity and mortality as a result, or conversely, an overdiagnosis in men. In this context, it is important to analyze the expression and enrichment of genes with associated phenotypes and disease-causing variants among high-risk CVD populations. Methods We performed RNA sequencing focusing on key CVD genes with a great number of genetic associations to HF. Peripheral blood samples were collected from a broad age range of adult male and female CVD patients. These patients were clinically diagnosed with CVDs and CMS/HCC HF, as well as including cardiomyopathy, hypertension, obesity, diabetes, asthma, high cholesterol, hernia, chronic kidney, joint pain, dizziness and giddiness, osteopenia of multiple sites, chest pain, osteoarthritis, and other diseases. Results We report RNA-seq driven case–control study to analyze patterns of expression in genes and differentiating the pathways, which differ between healthy and diseased patients. Our in-depth gene expression and enrichment analysis of RNA-seq data from patients with mostly HF and other CVDs on differentially expressed genes and CVD annotated genes revealed 4,885 differentially expressed genes (DEGs) and regulation of 41 genes known for HF and 23 genes related to other CVDs, with 15 DEGs as significantly expressed including four genes already known (FLNA, CST3, LGALS3, and HBA1) for HF and CVDs with the enrichment of many pathways. Furthermore, gender and ethnic group specific analysis showed shared and unique genes between the genders, and among different races. Broadening the scope of the results in clinical settings, we have linked the CVD genes with ICD codes. Conclusions Many pathways were found to be enriched, and gender-specific analysis showed shared and unique genes between the genders. Additional testing of these genes may lead to the development of new clinical tools to improve diagnosis and prognosis of CVD patients.Zeeshan AhmedSaman ZeeshanBruce T. LiangBMCarticleCardiovascularDiseaseExpressionEnrichmentGeneHeart failureMedicineRGeneticsQH426-470ENHuman Genomics, Vol 15, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cardiovascular Disease Expression Enrichment Gene Heart failure Medicine R Genetics QH426-470
spellingShingle	Cardiovascular Disease Expression Enrichment Gene Heart failure Medicine R Genetics QH426-470 Zeeshan Ahmed Saman Zeeshan Bruce T. Liang RNA-seq driven expression and enrichment analysis to investigate CVD genes with associated phenotypes among high-risk heart failure patients
description	Abstract Background Heart failure (HF) is one of the most common complications of cardiovascular diseases (CVDs) and among the leading causes of death in the US. Many other CVDs can lead to increased mortality as well. Investigating the genetic epidemiology and susceptibility to CVDs is a central focus of cardiology and biomedical life sciences. Several studies have explored expression of key CVD genes specially in HF, yet new targets and biomarkers for early diagnosis are still missing to support personalized treatment. Lack of gender-specific cardiac biomarker thresholds in men and women may be the reason for CVD underdiagnosis in women, and potentially increased morbidity and mortality as a result, or conversely, an overdiagnosis in men. In this context, it is important to analyze the expression and enrichment of genes with associated phenotypes and disease-causing variants among high-risk CVD populations. Methods We performed RNA sequencing focusing on key CVD genes with a great number of genetic associations to HF. Peripheral blood samples were collected from a broad age range of adult male and female CVD patients. These patients were clinically diagnosed with CVDs and CMS/HCC HF, as well as including cardiomyopathy, hypertension, obesity, diabetes, asthma, high cholesterol, hernia, chronic kidney, joint pain, dizziness and giddiness, osteopenia of multiple sites, chest pain, osteoarthritis, and other diseases. Results We report RNA-seq driven case–control study to analyze patterns of expression in genes and differentiating the pathways, which differ between healthy and diseased patients. Our in-depth gene expression and enrichment analysis of RNA-seq data from patients with mostly HF and other CVDs on differentially expressed genes and CVD annotated genes revealed 4,885 differentially expressed genes (DEGs) and regulation of 41 genes known for HF and 23 genes related to other CVDs, with 15 DEGs as significantly expressed including four genes already known (FLNA, CST3, LGALS3, and HBA1) for HF and CVDs with the enrichment of many pathways. Furthermore, gender and ethnic group specific analysis showed shared and unique genes between the genders, and among different races. Broadening the scope of the results in clinical settings, we have linked the CVD genes with ICD codes. Conclusions Many pathways were found to be enriched, and gender-specific analysis showed shared and unique genes between the genders. Additional testing of these genes may lead to the development of new clinical tools to improve diagnosis and prognosis of CVD patients.
format	article
author	Zeeshan Ahmed Saman Zeeshan Bruce T. Liang
author_facet	Zeeshan Ahmed Saman Zeeshan Bruce T. Liang
author_sort	Zeeshan Ahmed
title	RNA-seq driven expression and enrichment analysis to investigate CVD genes with associated phenotypes among high-risk heart failure patients
title_short	RNA-seq driven expression and enrichment analysis to investigate CVD genes with associated phenotypes among high-risk heart failure patients
title_full	RNA-seq driven expression and enrichment analysis to investigate CVD genes with associated phenotypes among high-risk heart failure patients
title_fullStr	RNA-seq driven expression and enrichment analysis to investigate CVD genes with associated phenotypes among high-risk heart failure patients
title_full_unstemmed	RNA-seq driven expression and enrichment analysis to investigate CVD genes with associated phenotypes among high-risk heart failure patients
title_sort	rna-seq driven expression and enrichment analysis to investigate cvd genes with associated phenotypes among high-risk heart failure patients
publisher	BMC
publishDate	2021
url	https://doaj.org/article/f0149186e0b14a1a9d7c8e309e28bd3d
work_keys_str_mv	AT zeeshanahmed rnaseqdrivenexpressionandenrichmentanalysistoinvestigatecvdgeneswithassociatedphenotypesamonghighriskheartfailurepatients AT samanzeeshan rnaseqdrivenexpressionandenrichmentanalysistoinvestigatecvdgeneswithassociatedphenotypesamonghighriskheartfailurepatients AT brucetliang rnaseqdrivenexpressionandenrichmentanalysistoinvestigatecvdgeneswithassociatedphenotypesamonghighriskheartfailurepatients
_version_	1718429381217484800

RNA-seq driven expression and enrichment analysis to investigate CVD genes with associated phenotypes among high-risk heart failure patients

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