DOI: 10.5061/dryad.47d7wm3ns
title: Cross-species analysis of genetic architecture and polygenic risk scores for non-contact ACL rupture in dogs and humans

description: 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.
description: # 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](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.