Aims: To see if an association exists between quantitative MRI biomarkers in the ACL and specific genetic variants. Once we have a number of genetic candidates, we aim to generate a polygenic risk score or simply use specific SNPs to predict primary or secondary ACL injury.
Scientific rationale: There have been a multitude of successful qMRI studies (performed by our group) which have predicted ACL outcomes. Additionally, there is substantial evidence that ACL health is associated with specific genetic loci and/or SNPs. Previous UK Biobank endeavors in this area have tested for genetic associations with ACL injuries, but the minimal occurence of primary ACL injury in the UK Biobank cohort means the dataset would be better leveraged to assess to ACL integrity instead. Therefore, we are justified in setting out to evaluate how much of the phenotypic variation in ACL integrity can be explained by certain genetic variants.
Duration: Quantifying the MRI data should take between 4-6 months. Once the qMRI data has been processed/generated, the GWAS should take an additional 1-3 months. Writing up the results will take a variable amount of time but ideally less than 2-4 months.
Impact: No knee ligament integrity study of this magnitude has been performed in humans. This will be the first human GWAS study to analyze ligament integrity, and the results could set the foundation for predicting which patients are more likely to injure their ACLs or accrue greater benefits from ACL surgery. Being able to predict such outcomes would revolutionize orthopedic practices in every hospital across the globe, as ACL injuries are one of the most common injuries necessitating surgery.