Genetics of musculoskeletal soft tissue injuries: Current status, challenges, and future directions

Abstract The evidence implicating genetics in the susceptibility to musculoskeletal soft tissue injuries is growing, with over 80 risk-conferring loci discovered to date. Primarily through the application of candidate gene studies, researchers have highlighted some of the critical extracellular matrix proteins and biological pathways underpinning matrix remodeling proposed to influence injury susceptibility. However, many of these loci have yet to be repeated in independent cohorts. Moreover, limited functional data is available at present to support the implicated genomic regions. Recent technologies have enabled researchers to explore the genome more broadly, though these studies are limited by the unavailability of large groups of well-defined cases and controls. It is essential that researchers collaborate to unravel the complexities of matrix remodeling, tissue capacity, and thereby improve our understanding of injury susceptibility. Through the establishment of international consortia, large cohorts can be attained to aid the identification of clinically relevant loci and molecules that may be targeted for therapeutic applications.