Genetics of adolescent idiopathic scoliosis in the post-genome-wide association study era

Recently, analyses of a genome-wide association study (GWAS) conducted in a Japanese population found several common susceptibility variants associated with adolescent idiopathic scoliosis (AIS) (1-3). The top variants identified from this GWAS reside in genomic regions with potentially etiologically relevant genes and have been replicated across multiple populations and ethnicities. As a result, genes involved in biological pathways that are now viewed as promising targets for downstream functional investigation include abnormal somatosensory function (LBX1) (1), delayed ossification of the developing spine (GPR126) (2), skeletal dysplasia (SOX9) (3) and scoliosis associated with syndromic disease (KCNJ2) (3), One of these variants, a single nucleotide polymorphism (SNP) in the 3’-flanking region of the LBX1 gene (rs11190878) (1), has been consistently replicated in several independent populations (4). Other GWASes have also identified novel AIS-associated variants, with some overlap among the top ranked SNPs, including rs11190878 (Albertsen et al., 2014, ASHG conference abstract) (5).