Cross-species analysis of genetic architecture and polygenic risk scores for non-contact ACL rupture in dogs and humans
Abstract Non-contact anterior cruciate ligament (ACL) rupture is a common serious orthopaedic disease in humans and dogs. Familial risk has been recognized in both species but interactions between genetic effects and environmental risk are not understood. We investigated ACL rupture heritability, ge...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07395-9 |
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| author | Mehdi Momen Hannah K. Kearney Margaret M. Patterson Susannah J. Sample Zijie Zhao Qiongshi Lu Guilherme J. M. Rosa Peter Muir |
| author_facet | Mehdi Momen Hannah K. Kearney Margaret M. Patterson Susannah J. Sample Zijie Zhao Qiongshi Lu Guilherme J. M. Rosa Peter Muir |
| author_sort | Mehdi Momen |
| collection | DOAJ |
| description | Abstract Non-contact anterior cruciate ligament (ACL) rupture is a common serious orthopaedic disease in humans and dogs. Familial risk has been recognized in both species but interactions between genetic effects and environmental risk are not understood. We investigated ACL rupture heritability, genetic architecture, selection pressure, sharing of risk genes and biological pathways, and polygenic risk score (PRS) prediction of disease risk. In both species, ACL rupture has moderate heritability, is likely under negative selection, and has a highly polygenic architecture where thousands of variant effects act together to influence disease risk. In dogs, we found hotspots of regional heritability. We also confirmed sharing of multiple risk genes. Our findings challenge the dogma that non-contact ACL rupture is predominantly due to a single overload injury event. Our results also suggest that accurate PRS prediction of ACL rupture risk is an achievable goal in both species, enabling identification of individuals for personalized medical care. |
| format | Article |
| id | doaj-art-952ca984d03743dd89a0ff298f6cdb79 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-952ca984d03743dd89a0ff298f6cdb792025-01-12T12:35:35ZengNature PortfolioCommunications Biology2399-36422025-01-018111210.1038/s42003-024-07395-9Cross-species analysis of genetic architecture and polygenic risk scores for non-contact ACL rupture in dogs and humansMehdi Momen0Hannah K. Kearney1Margaret M. Patterson2Susannah J. Sample3Zijie Zhao4Qiongshi Lu5Guilherme J. M. Rosa6Peter Muir7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-MadisonDepartment of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-MadisonDepartment of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-MadisonDepartment of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-MadisonDepartment of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin-MadisonDepartment of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin-MadisonDepartment of Animal and Dairy Sciences, College of Agriculture and Life Sciences, University of Wisconsin-MadisonDepartment of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-MadisonAbstract Non-contact anterior cruciate ligament (ACL) rupture is a common serious orthopaedic disease in humans and dogs. Familial risk has been recognized in both species but interactions between genetic effects and environmental risk are not understood. We investigated ACL rupture heritability, genetic architecture, selection pressure, sharing of risk genes and biological pathways, and polygenic risk score (PRS) prediction of disease risk. In both species, ACL rupture has moderate heritability, is likely under negative selection, and has a highly polygenic architecture where thousands of variant effects act together to influence disease risk. In dogs, we found hotspots of regional heritability. We also confirmed sharing of multiple risk genes. Our findings challenge the dogma that non-contact ACL rupture is predominantly due to a single overload injury event. Our results also suggest that accurate PRS prediction of ACL rupture risk is an achievable goal in both species, enabling identification of individuals for personalized medical care.https://doi.org/10.1038/s42003-024-07395-9 |
| spellingShingle | Mehdi Momen Hannah K. Kearney Margaret M. Patterson Susannah J. Sample Zijie Zhao Qiongshi Lu Guilherme J. M. Rosa Peter Muir Cross-species analysis of genetic architecture and polygenic risk scores for non-contact ACL rupture in dogs and humans Communications Biology |
| title | Cross-species analysis of genetic architecture and polygenic risk scores for non-contact ACL rupture in dogs and humans |
| title_full | Cross-species analysis of genetic architecture and polygenic risk scores for non-contact ACL rupture in dogs and humans |
| title_fullStr | Cross-species analysis of genetic architecture and polygenic risk scores for non-contact ACL rupture in dogs and humans |
| title_full_unstemmed | Cross-species analysis of genetic architecture and polygenic risk scores for non-contact ACL rupture in dogs and humans |
| title_short | Cross-species analysis of genetic architecture and polygenic risk scores for non-contact ACL rupture in dogs and humans |
| title_sort | cross species analysis of genetic architecture and polygenic risk scores for non contact acl rupture in dogs and humans |
| url | https://doi.org/10.1038/s42003-024-07395-9 |
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