Genetic association of complex traits: using idiopathic scoliosis as an example

Although the exact etiology of adolescent idiopathic scoliosis is still undefined, genetic factors play an important role. Some patients have familial genetic disease that appears to have an autosomal dominant pattern. Linkage studies of these families revealed multiple potential genetic loci that may predispose individuals to the condition. Additional genetic analysis is required to identify the disease-predisposition genes of the loci found in the linkage studies. The initial localization of potential critical loci through large family-based population studies now needs fine mapping by association studies using high-density polymorphic markers (single nucleotide polymorphisms or SNPs). These markers are now available as a result of the Human Genome Project, International HapMap Project, and other genetic diversity projects. The application of this emerging data in a large association study of affected individuals and controls is integral for the identification of putative genes. With these complementary approaches, we will be able to progress with mutational analysis of hopefully a small set of candidate genes in the near future. In this commentary, we illustrate what is possible in the genomic era, and indicate what we should expect from genetic studies in adolescent idiopathic scoliosis, a complex trait disease.