Genetic Basis of Intervertebral Disc Degeneration

Abstract

Genetics is an area of study that connects genes with functions, variations with phenotypes, and, of most interest to scientists and clinicians, mutations with diseases. According to the Online Mendelian Inheritance in Man (OMIM), an online catalog for human genes and Mendelian disorders, over 3,000 known “genotype-phenotype” pairs have been recorded. A direct application of such knowledge is diagnosis, of which prenatal testing and newborn screening of rare conditions are common nowadays; ideally, this would be extended in future for disease prevention or the development of personalized medicine. It is clear that our understanding of disease mechanism of rare skeletal disorders such as osteogenesis imperfecta (OI), spondyloepiphyseal dysplasia (SED), achondroplasia, and Ehlers-Danlos syndrome (EDS) has come directly from knowing the genes involved, allowing detailed in vitro and in vivo functional studies. While more difficult for common disorders such as intervertebral disc degeneration, the same principle can be applied, bearing in mind the effect size, the number of genes involved, and contributions from environment factors. These are the issues that this chapter will address systematically, namely, to provide the basic concepts of what genetic studies can achieve and with the benefit of hindsight from studies of similar disorders such as osteoarthritis (OA) to generate a road map for studies of intervertebral disc degeneration.