A genome-wide association study on hematopoietic stem cell transplantation reveals novel genomic loci associated with transplant outcomes
IntroductionData on genomic susceptibility for adverse outcomes after hematopoietic stem cell transplantation (HSCT) for recipients are scarce.MethodsWe performed a genome wide association study (GWAS) to identify genes associated with survival/mortality, relapse, and severe graft-versus-host diseas...
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1280876/full |
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| author | Albert Rosenberger Rachel E. Crossland Ralf Dressel Dieter Kube Daniel Wolff Gerald Wulf Heike Bickeböller Anne Dickinson Ernst Holler |
| author_facet | Albert Rosenberger Rachel E. Crossland Ralf Dressel Dieter Kube Daniel Wolff Gerald Wulf Heike Bickeböller Anne Dickinson Ernst Holler |
| author_sort | Albert Rosenberger |
| collection | DOAJ |
| description | IntroductionData on genomic susceptibility for adverse outcomes after hematopoietic stem cell transplantation (HSCT) for recipients are scarce.MethodsWe performed a genome wide association study (GWAS) to identify genes associated with survival/mortality, relapse, and severe graft-versus-host disease (sGvHD), fitting proportional hazard and subdistributional models to data of n=1,392 recipients of European ancestry from three centres.ResultsThe single nucleotide polymorphism (SNP) rs17154454, intronic to the neuronal growth guidant semaphorin 3C gene (SEMA3C), was genome-wide significantly associated with event-free survival (p=7.0x10-8) and sGvHD (p=7.5x10-8). Further associations were detected for SNPs in the Paxillin gene (PXN) with death without prior relapse or sGvHD, as well as for SNPs of the Plasmacytoma Variant Translocation 1 gene (PVT1, a long non-coding RNA gene), the Melanocortin 5 Receptor (MC5R) gene and the WW Domain Containing Oxidoreductase gene (WWOX), all associated with the occurrence of sGvHD. Functional considerations support the observed associations.DiscussionThus, new genes were identified, potentially influencing the outcome of HSCT. |
| first_indexed | 2024-03-08T05:11:52Z |
| format | Article |
| id | doaj.art-28fe5289e59f467c9ac274bb9c1be77a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T05:11:52Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-28fe5289e59f467c9ac274bb9c1be77a2024-02-07T05:31:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.12808761280876A genome-wide association study on hematopoietic stem cell transplantation reveals novel genomic loci associated with transplant outcomesAlbert Rosenberger0Rachel E. Crossland1Ralf Dressel2Dieter Kube3Daniel Wolff4Gerald Wulf5Heike Bickeböller6Anne Dickinson7Ernst Holler8Department of Genetic Epidemiology, University Medical Center, Georg August University Göttingen, Göttingen, GermanyTranslational & Clinical Research Institute, Faculty of Medical Science, Medical School, Newcastle University, Newcastle upon Tyne, United KingdomDepartment of Cellular and Molecular Immunology, University Medical Center, Georg August University Göttingen, Göttingen, GermanyDepartment of Cellular and Molecular Immunology, University Medical Center, Georg August University Göttingen, Göttingen, GermanyDepartment of Internal Medicine III, University Hospital Regensburg, Regensburg, GermanyHematology and Medical Oncology, University Medical Center, Georg August University Göttingen, Göttingen, GermanyDepartment of Genetic Epidemiology, University Medical Center, Georg August University Göttingen, Göttingen, GermanyTranslational & Clinical Research Institute, Faculty of Medical Science, Medical School, Newcastle University, Newcastle upon Tyne, United KingdomDepartment of Internal Medicine III, University Hospital Regensburg, Regensburg, GermanyIntroductionData on genomic susceptibility for adverse outcomes after hematopoietic stem cell transplantation (HSCT) for recipients are scarce.MethodsWe performed a genome wide association study (GWAS) to identify genes associated with survival/mortality, relapse, and severe graft-versus-host disease (sGvHD), fitting proportional hazard and subdistributional models to data of n=1,392 recipients of European ancestry from three centres.ResultsThe single nucleotide polymorphism (SNP) rs17154454, intronic to the neuronal growth guidant semaphorin 3C gene (SEMA3C), was genome-wide significantly associated with event-free survival (p=7.0x10-8) and sGvHD (p=7.5x10-8). Further associations were detected for SNPs in the Paxillin gene (PXN) with death without prior relapse or sGvHD, as well as for SNPs of the Plasmacytoma Variant Translocation 1 gene (PVT1, a long non-coding RNA gene), the Melanocortin 5 Receptor (MC5R) gene and the WW Domain Containing Oxidoreductase gene (WWOX), all associated with the occurrence of sGvHD. Functional considerations support the observed associations.DiscussionThus, new genes were identified, potentially influencing the outcome of HSCT.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1280876/fullHSCTGvHDGWASsurvivalcompeting risks |
| spellingShingle | Albert Rosenberger Rachel E. Crossland Ralf Dressel Dieter Kube Daniel Wolff Gerald Wulf Heike Bickeböller Anne Dickinson Ernst Holler A genome-wide association study on hematopoietic stem cell transplantation reveals novel genomic loci associated with transplant outcomes Frontiers in Immunology HSCT GvHD GWAS survival competing risks |
| title | A genome-wide association study on hematopoietic stem cell transplantation reveals novel genomic loci associated with transplant outcomes |
| title_full | A genome-wide association study on hematopoietic stem cell transplantation reveals novel genomic loci associated with transplant outcomes |
| title_fullStr | A genome-wide association study on hematopoietic stem cell transplantation reveals novel genomic loci associated with transplant outcomes |
| title_full_unstemmed | A genome-wide association study on hematopoietic stem cell transplantation reveals novel genomic loci associated with transplant outcomes |
| title_short | A genome-wide association study on hematopoietic stem cell transplantation reveals novel genomic loci associated with transplant outcomes |
| title_sort | genome wide association study on hematopoietic stem cell transplantation reveals novel genomic loci associated with transplant outcomes |
| topic | HSCT GvHD GWAS survival competing risks |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1280876/full |
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