First Report of Evaluation of Variant rs11190870 nearby LBX1 Gene with Adolescent Idiopathic Scoliosis Susceptibility in a South-Asian Indian Population

Abstract

LBX1 is a developmental gene involved in skeletal muscle development and somatosensory functioning and proven to be an important gene involved in Adolescent Idiopathic Scoliosis (AIS) etiology. Variant rs11190870 is located 7.5 kb downstream of LBX1 gene and is part of haplotype that is reported to provide risk for AIS. Several studies, including various Genome Wide Association, replication and meta-analyses studies have implicated its association with AIS in different populations. However, any such study is altogether lacking in South-Asian Indian populations. In this first genetic association study for AIS from the region, we tried to replicate association of variant rs11190870 in 95 AIS cases and 282 healthy non-AIS controls from Northwest India. The genotyping was carried out on a Realtime PCR using TaqMan allele discrimination assay and the variant was found to be following Hardy Weinberg equilibrium. The statistical analyses of the genotyping data did not show significant association (p=0.66) of variant rs11190870 with AIS in the population of Northwest India. The results are interesting findings in a population that has never been studied before for AIS susceptibility. However, the findings can be attributed to under power study thus, need evaluation in a large sample set from the population. Interestingly, frequency distribution of the variant in Indian control population datasets was found to be different than other global populations. Linkage Disequilibrium (LD) differences in the genomic region were also observed in these populations while analysing 1000Genomes phase 3 data. It hints at existence of either haplotypic differences in LBX1 locus in South-Asian Indian populations with respect to other populations or genetic heterogeneity in AIS susceptibility. This lays a foundation for genome wide association study (GWAS) in Indian populations cohort, for better understanding of AIS, a task we are pursuing.