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

Abstract

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).