Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity, 
affecting around 2% of adolescents worldwide. Genetic factors play an important 
role in its etiology. Using a genome-wide association study (GWAS), we recently 
identified novel AIS susceptibility loci on chromosomes 10q24.31 and 6q24.1. To 
identify more AIS susceptibility loci relating to its severity and progression, 
we performed GWAS by limiting the case subjects to those with severe AIS. 
Through a two-stage association study using a total of ∼12,000 Japanese 
subjects, we identified a common variant, rs12946942 that showed a significant 
association with severe AIS in the recessive model (P=4.00 × 10(-8), odds ratio 
[OR]=2.05). Its association was replicated in a Chinese population (combined 
P=6.43 × 10(-12), OR = 2.21). rs12946942 is on chromosome 17q24.3 near the genes 
SOX9 and KCNJ2, which when mutated cause scoliosis phenotypes. Our findings will 
offer new insight into the etiology and progression of AIS.