Understanding the Basis of Genetic Studies: Adolescent Idiopathic Scoliosis as an Example

Abstract

Study design: A review of the general concepts of genetics studies with specific reference to adolescent idiopathic scoliosis (AIS).

Objectives: To equip the average spine surgeon with the vocabulary and understanding needed to understand the genetics of scoliosis and the approaches used to identify risk genes.

Summary of background data: Adolescent idiopathic scoliosis is a multifactorial disease. Increasing evidence from families and monozygotic twins suggests the involvement of genetic factors. An estimation of heritability also indicates a strong influence of genetics on the disease. Increasing focus has been placed on identifying genes and genetic variants associated with AIS.

Review: This is a review of genes and genetic variations, the phenotype definition of AIS in genetics studies, concepts and approaches to identifying associated genes, and the evaluation of results. Different types of genetic variations are present in the genome. These variations may modulate the expression or function of protein products, which in turn alter individuals' susceptibility to disease. Identifying the variants related to AIS requires an objective and clearly defined phenotype, among which the Cobb angle is commonly used. The phenotype helps classify subjects into cases and controls. By selecting candidate genes of growth factors and hormonal receptors, which are speculated to be involved in the mechanism of disease, the variants within these genes were compared between cases and controls to identify any differences. Another approach was to use large families and inspect the co-segregation of variants and phenotypes. Recently, arrays covering the variants of the whole genome were developed and assist in high-throughput screening for associated genes.

Conclusions: Genetic factors have an important role in AIS. Deciphering the genes and genetic variants associated with AIS can improve our understanding of the mechanisms of the disease, as well as assist in designing treatment methods and preventive measures.

Keywords: Adolescent idiopathic scoliosis; Association studies; Genetics; Linkage.