Linking single nucleotide polymorphisms to signaling blueprints in abdominal aortic aneurysms
Abstract Abdominal aortic aneurysms (AAA) is a multifactorial complex disease with life-threatening consequences. While Genome-wide association studies (GWAS) have revealed several single nucleotide polymorphisms (SNPs) located in the genome of individuals with AAA, the link between SNPs with the as...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-25144-y |
| _version_ | 1811203588742971392 |
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| author | Chrysania Lim Muhammad Yogi Pratama Cristobal Rivera Michele Silvestro Philip S. Tsao Lars Maegdefessel Katherine A. Gallagher Thomas Maldonado Bhama Ramkhelawon |
| author_facet | Chrysania Lim Muhammad Yogi Pratama Cristobal Rivera Michele Silvestro Philip S. Tsao Lars Maegdefessel Katherine A. Gallagher Thomas Maldonado Bhama Ramkhelawon |
| author_sort | Chrysania Lim |
| collection | DOAJ |
| description | Abstract Abdominal aortic aneurysms (AAA) is a multifactorial complex disease with life-threatening consequences. While Genome-wide association studies (GWAS) have revealed several single nucleotide polymorphisms (SNPs) located in the genome of individuals with AAA, the link between SNPs with the associated pathological signals, the influence of risk factors on their distribution and their combined analysis is not fully understood. We integrated 86 AAA SNPs from GWAS and clinical cohorts from the literature to determine their phenotypical vulnerabilities and association with AAA risk factors. The SNPs were annotated using snpXplorer AnnotateMe tool to identify their chromosomal position, minor allele frequency, CADD (Combined Annotation Dependent Depletion), annotation-based pathogenicity score, variant consequence, and their associated gene. Gene enrichment analysis was performed using Gene Ontology and clustered using REVIGO. The plug-in GeneMANIA in Cytoscape was applied to identify network integration with associated genes and functions. 15 SNPs affecting 20 genes with a CADD score above ten were identified. AAA SNPs were predominantly located on chromosome 3 and 9. Stop-gained rs5516 SNP obtained high frequency in AAA and associated with proinflammatory and vascular remodeling phenotypes. SNPs presence positively correlated with hypertension, dyslipidemia and smoking history. GO showed that AAA SNPs and their associated genes could regulate lipid metabolism, extracellular matrix organization, smooth muscle cell proliferation, and oxidative stress, suggesting that part of these AAA traits could stem from genetic abnormalities. We show a library of inborn SNPs and associated genes that manifest in AAA. We uncover their pathological signaling trajectories that likely fuel AAA development. |
| first_indexed | 2024-04-12T02:57:52Z |
| format | Article |
| id | doaj.art-f5bafe9c65b74125b9aa1f0ca3f66e82 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T02:57:52Z |
| publishDate | 2022-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f5bafe9c65b74125b9aa1f0ca3f66e822022-12-22T03:50:46ZengNature PortfolioScientific Reports2045-23222022-12-0112111310.1038/s41598-022-25144-yLinking single nucleotide polymorphisms to signaling blueprints in abdominal aortic aneurysmsChrysania Lim0Muhammad Yogi Pratama1Cristobal Rivera2Michele Silvestro3Philip S. Tsao4Lars Maegdefessel5Katherine A. Gallagher6Thomas Maldonado7Bhama Ramkhelawon8Division of Vascular and Endovascular Surgery, Department of Surgery, New York University Langone Medical CenterDivision of Vascular and Endovascular Surgery, Department of Surgery, New York University Langone Medical CenterDivision of Vascular and Endovascular Surgery, Department of Surgery, New York University Langone Medical CenterDivision of Vascular and Endovascular Surgery, Department of Surgery, New York University Langone Medical CenterVA Palo Alto Health Care SystemDepartment of Vascular and Endovascular Surgery, Technical University MunichDepartment of Surgery, University of MichiganDivision of Vascular and Endovascular Surgery, Department of Surgery, New York University Langone Medical CenterDivision of Vascular and Endovascular Surgery, Department of Surgery, New York University Langone Medical CenterAbstract Abdominal aortic aneurysms (AAA) is a multifactorial complex disease with life-threatening consequences. While Genome-wide association studies (GWAS) have revealed several single nucleotide polymorphisms (SNPs) located in the genome of individuals with AAA, the link between SNPs with the associated pathological signals, the influence of risk factors on their distribution and their combined analysis is not fully understood. We integrated 86 AAA SNPs from GWAS and clinical cohorts from the literature to determine their phenotypical vulnerabilities and association with AAA risk factors. The SNPs were annotated using snpXplorer AnnotateMe tool to identify their chromosomal position, minor allele frequency, CADD (Combined Annotation Dependent Depletion), annotation-based pathogenicity score, variant consequence, and their associated gene. Gene enrichment analysis was performed using Gene Ontology and clustered using REVIGO. The plug-in GeneMANIA in Cytoscape was applied to identify network integration with associated genes and functions. 15 SNPs affecting 20 genes with a CADD score above ten were identified. AAA SNPs were predominantly located on chromosome 3 and 9. Stop-gained rs5516 SNP obtained high frequency in AAA and associated with proinflammatory and vascular remodeling phenotypes. SNPs presence positively correlated with hypertension, dyslipidemia and smoking history. GO showed that AAA SNPs and their associated genes could regulate lipid metabolism, extracellular matrix organization, smooth muscle cell proliferation, and oxidative stress, suggesting that part of these AAA traits could stem from genetic abnormalities. We show a library of inborn SNPs and associated genes that manifest in AAA. We uncover their pathological signaling trajectories that likely fuel AAA development.https://doi.org/10.1038/s41598-022-25144-y |
| spellingShingle | Chrysania Lim Muhammad Yogi Pratama Cristobal Rivera Michele Silvestro Philip S. Tsao Lars Maegdefessel Katherine A. Gallagher Thomas Maldonado Bhama Ramkhelawon Linking single nucleotide polymorphisms to signaling blueprints in abdominal aortic aneurysms Scientific Reports |
| title | Linking single nucleotide polymorphisms to signaling blueprints in abdominal aortic aneurysms |
| title_full | Linking single nucleotide polymorphisms to signaling blueprints in abdominal aortic aneurysms |
| title_fullStr | Linking single nucleotide polymorphisms to signaling blueprints in abdominal aortic aneurysms |
| title_full_unstemmed | Linking single nucleotide polymorphisms to signaling blueprints in abdominal aortic aneurysms |
| title_short | Linking single nucleotide polymorphisms to signaling blueprints in abdominal aortic aneurysms |
| title_sort | linking single nucleotide polymorphisms to signaling blueprints in abdominal aortic aneurysms |
| url | https://doi.org/10.1038/s41598-022-25144-y |
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