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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| Format: | Article |
| Language: | English |
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BMC
2021-11-01
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| Series: | Human Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40246-021-00367-8 |
| _version_ | 1798000010069016576 |
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| author | Zeeshan Ahmed Saman Zeeshan Bruce T. Liang |
| author_facet | Zeeshan Ahmed Saman Zeeshan Bruce T. Liang |
| author_sort | Zeeshan Ahmed |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T11:13:27Z |
| format | Article |
| id | doaj.art-f0149186e0b14a1a9d7c8e309e28bd3d |
| institution | Directory Open Access Journal |
| issn | 1479-7364 |
| language | English |
| last_indexed | 2024-04-11T11:13:27Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Human Genomics |
| spelling | doaj.art-f0149186e0b14a1a9d7c8e309e28bd3d2022-12-22T04:27:23ZengBMCHuman Genomics1479-73642021-11-0115111810.1186/s40246-021-00367-8RNA-seq driven expression and enrichment analysis to investigate CVD genes with associated phenotypes among high-risk heart failure patientsZeeshan Ahmed0Saman Zeeshan1Bruce T. Liang2Rutgers Institute for Health, Health Care Policy and Aging Research, Rutgers UniversityRutgers Cancer Institute of New Jersey, Rutgers UniversityPat and Jim Calhoun Cardiology Center, UConn School of Medicine, University of Connecticut Health CenterAbstract 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.https://doi.org/10.1186/s40246-021-00367-8CardiovascularDiseaseExpressionEnrichmentGeneHeart failure |
| spellingShingle | 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 Human Genomics Cardiovascular Disease Expression Enrichment Gene Heart failure |
| title | 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_short | 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 |
| topic | Cardiovascular Disease Expression Enrichment Gene Heart failure |
| url | https://doi.org/10.1186/s40246-021-00367-8 |
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