CORR Insights ®: Are copy number variants associated with adolescent idiopathic scoliosis?

Abstract

A dolescent idiopathic scoliosis (AIS) is a genetically heterogeneous complex condition that affects approximately 3% of the population. Although genome-wide association studies have pointed us towards candidate loci for genetic causes of this condition, it is evident that these loci do not constitute the majority of AIS heritability. Since copy number variation has been associated with the presence of birth defects, neuropsychiatric disabilities, congenital heart disease, and skeletal disorders such as clubfoot, Buchan et al. theorized that rare copy number variants contribute to the pathogenesis of scoliosis. In their study, Buchan et al. identified clinically significant copy number variation with a size of 125kb or greater having at least 50 markers using the Affymetrix Genome wide SNP array 6.0 in nine of 143 (6.3%) patients with AIS. These included proximal duplications of 1q21.1 (Thrombocytopenia Absent Radius syndrome region); 2q13, 15q11.2, and 16p11.2 deletions. Trisomy X was identified in two of 114 (1.8%) females with AIS. The 1q21.1 variant appeared to have reduced penetrance. These rare and novel copy number variations were observed with a greater frequency in the AIS population compared to a control population derived from 1079 individuals of European-American ancestry, which included individuals with bipolar disorder and idiopathic clubfoot. It is noteworthy that three of the observed copy number variations are associated with bone phenotypes including 1q21.1 (radial abnormalities), 15q11.2 duplications (hemivertebrae), and Trisomy X (scoliosis).