Cross-species analysis of genetic architecture and polygenic risk scores for non-contact ACL rupture in dogs and humans
Data files
Dec 28, 2024 version files 47.65 MB
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acl_1006_Lab.dryad.bed
35.80 MB
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acl_1006_Lab.dryad.bim
4.55 MB
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acl_1006_Lab.dryad.fam
26.06 KB
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acl_108_Rott.dryad.bed
3.32 MB
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acl_108_Rott.dryad.bim
3.94 MB
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acl_108_Rott.dryad.fam
2.48 KB
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README.md
1.27 KB
Abstract
Non-contact anterior cruciate ligament (ACL) rupture is a common heritable orthopaedic disease with serious long-term sequelae in humans and dogs, with many patients affected with moderate to severe osteoarthritis after diagnosis. The use of dog genetic data is a powerful approach to enrich human genome-wide association studies. Current clinical dogma views ACL rupture as an injury-driven event. Familial risk has been recognized in both species for many years. However, it is unclear how genetic effects interact with environmental risk to influence non-contact ACL rupture risk. We comprehensively investigated non-contact ACL rupture heritability, genetic architecture, genetic selective pressure, sharing of risk genes and biological pathways between two species, and polygenic risk score (PRS) prediction of disease risk. We confirmed moderate non-contact ACL rupture heritability in both species. In the dog model, hotspots of regional heritability were identified. We showed that non-contact ACL rupture is a disease under negative selection with a highly polygenic architecture in both species, with thousands of variant effects acting together to influence disease risk. Notably, we also confirmed the sharing of risk genes in the two species. Our findings challenge the dogma that non-contact ACL rupture is predominantly due to a single maneuver that catastrophically overloads the ACL. Despite the potential relevance of PRS prediction to orthopaedic disease, studies investigating its applicability are scarce. Our findings suggest that accurate PRS prediction of non-contact ACL rupture risk is an achievable research goal in both species. Clinical implementation would identify individuals for personalized medical and physical therapy care and lifestyle modification.
README: Cross-species analysis of genetic architecture and polygenic risk scores for non-contact ACL rupture in dogs and humans
https://doi.org/10.5061/dryad.47d7wm3ns
Each of the two datasets consists of a PLINK binary file set consisting of the SNP genotypes, a SNP map file, and a file describing the sex of the two populations of dogs. There is a file set for the Labrador Retriever and another one for the Rottweiler. The ACL rupture phenotypes are retained at the University of Wisconsin-Madison as proprietary.
Description of the data and file structure
all_108_Rott.dryad.fam
PLINK binary format fam file for 108 Rottweilers
all_108_Rott.dryad.bed
PLINK binary format bed file for 108 Rottweilers
all_108_Rott.dryad.bim
PLINK binary format bim file for 108 Rottweilers
all_1006_Lab.dryad.fam
PLINK binary format fam file for 1006 Labrador Retrievers
all_1006_Lab.dryad.bed
PLINK binary format bed file for 1006 Labrador Retrievers
all_106_Lab.dryad.bim
PLINK binary format bim file for 1006 Labrador Retrievers
Sharing/Access information
Not applicable
Code/Software
These PLINK binary files can be read using the PLINK software or other related software programs that read PLINK binary file sets.