Association between Common Variants near LBX1 and Adolescent Idiopathic Scoliosis Replicated in the Chinese Han Population

Abstract

BackgroundAdolescent idiopathic scoliosis (AIS) is one of the most common spinal deformities found in adolescent populations. Recently, a genome-wide association study (GWAS) in a Japanese population indicated that three single nucleotide polymorphisms (SNPs), rs11190870, rs625039 and rs11598564, all located near the LBX1 gene, may be associated with AIS susceptibility [1]. This study suggests a novel AIS predisposition candidate gene and supports the hypothesis that somatosensory functional disorders could contribute to the pathogenesis of AIS. These findings warrant replication in other populations.Methodology/Principal FindingsFirst, we conducted a case-control study consisting of 953 Chinese Han individuals from southern China (513 patients and 440 healthy controls), and the three SNPs were all found to be associated with AIS predisposition. The ORs were observed as 1.49 (95% CI 1.23–1.80, P = 5.09E-5), 1.70 (95% CI 1.42–2.04, P = 1.17E-8) and 1.52 (95% CI 1.27–1.83, P = 5.54E-6) for rs625039, rs11190870 and rs11598564, respectively. Second, a case-only study including a subgroup of AIS patients (N = 234) was performed to determine the effects of these variants on the severity of the condition. However, we did not find any association between these variants and the severity of curvature.ConclusionThis study shows that the genetic variants near the LBX1 gene are associated with AIS susceptibility in Chinese Han population. It successfully replicates the results of the GWAS, which was performed in a Japanese population.

Candidate gene analysis and exome sequencing confirm LBX1 as a susceptibility gene for idiopathic scoliosis

“…The variant rs11190870 seems to be associated to idiopathic scoliosis irrespective of scoliosis curve severity [28][29][30]. This is supported by our findings, where we found no substantial differences in OR between mild, moderate, or severe scoliosis compared with controls.…”

“…This association has subsequently been replicated in several North American and East Asian cohorts, suggesting the region on 10q24.31 harboring the LBX1 gene, to be a true susceptibility locus for idiopathic scoliosis [28][29][30]. In this study, we found a highly significant association of rs11190870 to idiopathic scoliosis also in a Scandinavian population, and as such, confirm the A1, allele 1 (risk allele); A2, allele 2; RAF, risk allele frequency; OR, odds ratio; CI, confidence interval; GPR126, G protein-coupled receptor; LBX1,ladybird homeobox 1; CHL1, cell adhesion molecule L1-like.…”

Rare coding variants in MAPK7 predispose to adolescent idiopathic scoliosis

“…genotyped using the MassArray system (Sequenom, San Diego, California) with primers of c.886G> A (Fwd: 5prepared by the Beijing Genomics Institute (Shenzhen, China), as described previously(Buetow et al, 2001;Gao et al, 2013).…”

Genetic Variations of Ultraconserved Elements in the Human Genome

“…Sequencing of positional candidate genes of a large family of Bulgarian descent revealed a missense mutation rs121434591 as a cause for vocal cord and pharyngeal weakness with distal myopathy (Senderek et al, 2009). rs11190870, an intergenic SNP located 6745 bp downstream of the Ladybird homeobox 1 gene (LBX1), is associated with adolescent idiopathic scoliosis (Chettier et al, 2015;Gao et al, 2013;Grauers et al, 2015;Jiang et al, 2013;Londono et al, 2014;Miyake et al, 2013;Takahashi et al, 2011).…”