Genetic analyses identify evidence for a causal relationship between Ewing sarcoma and hernias
Summary: Knowledge of Ewing sarcoma (EWS) risk factors is exceedingly limited; however, multiple small, independent studies have suggested a possible connection between hernia and EWS. By leveraging hernia summary statistics from the UK Biobank and a recently published genome-wide association study...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | HGG Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666247723000866 |
| _version_ | 1827753230240579584 |
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| author | Tianzhong Yang Lauren J. Mills Aubrey K. Hubbard Rui Cao Andrew Raduski Mitchell J. Machiela Logan G. Spector |
| author_facet | Tianzhong Yang Lauren J. Mills Aubrey K. Hubbard Rui Cao Andrew Raduski Mitchell J. Machiela Logan G. Spector |
| author_sort | Tianzhong Yang |
| collection | DOAJ |
| description | Summary: Knowledge of Ewing sarcoma (EWS) risk factors is exceedingly limited; however, multiple small, independent studies have suggested a possible connection between hernia and EWS. By leveraging hernia summary statistics from the UK Biobank and a recently published genome-wide association study of EWS (733 EWS cases and 1,346 controls), we conducted a genetic investigation of the relationship of 5 hernia types (diaphragmatic, inguinal, umbilical, femoral, and ventral) and EWS. We discovered a positive causal relationship between inguinal hernia and EWS (OR 1.27, 95% confidence interval [CI] 1.01–1.59, and p = 0.041) through Mendelian randomization analysis. Further analyses suggested shared pathways through three genes: HMGA2, LOX, and FBXW7. Diaphragmatic hernia showed a stronger causal relationship with EWS among all of the hernia types (OR 2.26, 95% CI 1.30–3.95, p = 0.004), but no statistically significant local correlation pattern was observed. No evidence of a causal or genetic relationship was observed between EWS and the other three hernia types, including umbilical hernia, despite a previous report indicating an OR as high as 3.3. The finding of our genetic analysis provided additional support to the hypothesis that EWS and hernias may share a common origin. |
| first_indexed | 2024-03-11T07:33:44Z |
| format | Article |
| id | doaj.art-4174c41eac61493c9d85b5d97c8878a5 |
| institution | Directory Open Access Journal |
| issn | 2666-2477 |
| language | English |
| last_indexed | 2024-03-11T07:33:44Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | HGG Advances |
| spelling | doaj.art-4174c41eac61493c9d85b5d97c8878a52023-11-17T05:28:12ZengElsevierHGG Advances2666-24772024-01-0151100254Genetic analyses identify evidence for a causal relationship between Ewing sarcoma and herniasTianzhong Yang0Lauren J. Mills1Aubrey K. Hubbard2Rui Cao3Andrew Raduski4Mitchell J. Machiela5Logan G. Spector6Division of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minneapolis, MN, USA; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USADepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USADivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892, USADivision of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minneapolis, MN, USADepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USADivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892, USADepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Corresponding authorSummary: Knowledge of Ewing sarcoma (EWS) risk factors is exceedingly limited; however, multiple small, independent studies have suggested a possible connection between hernia and EWS. By leveraging hernia summary statistics from the UK Biobank and a recently published genome-wide association study of EWS (733 EWS cases and 1,346 controls), we conducted a genetic investigation of the relationship of 5 hernia types (diaphragmatic, inguinal, umbilical, femoral, and ventral) and EWS. We discovered a positive causal relationship between inguinal hernia and EWS (OR 1.27, 95% confidence interval [CI] 1.01–1.59, and p = 0.041) through Mendelian randomization analysis. Further analyses suggested shared pathways through three genes: HMGA2, LOX, and FBXW7. Diaphragmatic hernia showed a stronger causal relationship with EWS among all of the hernia types (OR 2.26, 95% CI 1.30–3.95, p = 0.004), but no statistically significant local correlation pattern was observed. No evidence of a causal or genetic relationship was observed between EWS and the other three hernia types, including umbilical hernia, despite a previous report indicating an OR as high as 3.3. The finding of our genetic analysis provided additional support to the hypothesis that EWS and hernias may share a common origin.http://www.sciencedirect.com/science/article/pii/S2666247723000866diaphragmatic herniainguinal herniaEwing sarcomaMendelian randomizationgenome-wide association studyGWAS |
| spellingShingle | Tianzhong Yang Lauren J. Mills Aubrey K. Hubbard Rui Cao Andrew Raduski Mitchell J. Machiela Logan G. Spector Genetic analyses identify evidence for a causal relationship between Ewing sarcoma and hernias HGG Advances diaphragmatic hernia inguinal hernia Ewing sarcoma Mendelian randomization genome-wide association study GWAS |
| title | Genetic analyses identify evidence for a causal relationship between Ewing sarcoma and hernias |
| title_full | Genetic analyses identify evidence for a causal relationship between Ewing sarcoma and hernias |
| title_fullStr | Genetic analyses identify evidence for a causal relationship between Ewing sarcoma and hernias |
| title_full_unstemmed | Genetic analyses identify evidence for a causal relationship between Ewing sarcoma and hernias |
| title_short | Genetic analyses identify evidence for a causal relationship between Ewing sarcoma and hernias |
| title_sort | genetic analyses identify evidence for a causal relationship between ewing sarcoma and hernias |
| topic | diaphragmatic hernia inguinal hernia Ewing sarcoma Mendelian randomization genome-wide association study GWAS |
| url | http://www.sciencedirect.com/science/article/pii/S2666247723000866 |
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