Introduction

Adolescent idiopathic scoliosis (AIS) is the most common paediatric spinal deformity, affecting about 3% of school-aged children worldwide. This disorder occurs in otherwise healthy children who bear no obvious deficiencies in the components of the spinal column itself. The cause of AIS is poorly understood, as is implied by the name. Lesions of the bony composition of the vertebrae, the vertebral endplates, the paraspinous muscles, or the neurological system each have been proposed to explain disease pathogenesis. Progress has been hampered by the absence of an obvious AIS animal model. Consequently we have used genetic studies in human populations to identify factors underlying AIS susceptibility.

The complex inheritance and population frequency of AIS suggest that many genetic factors are involved in this disease. To search comprehensively for such factors we previously undertook the first genome-wide association study (GWAS) of AIS susceptibility in a cohort of 419 families in Texas, USA. We found that chromosome 3 SNPs in the proximity of the CHL1 gene yielded strongest results, which we replicated in additional cohorts (rs10510181 OR 1·49, 95% CI 1·29–173, p=2·58×10–8). CHL1 is of interest because it encodes an axon guidance protein and is functionally related to the ROBO3 gene that causes hereditary gaze palsy with progressive scoliosis (HGPPS), a rare disease marked by severe scoliosis. Here we expanded the study to 702 Texas families.