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

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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of Shri Mata Vaishno Devi University [Institutional Ethical Review Board (IERB) (IERB Serial No: SMVDU/IERB/18/69 and SMVDU/IERB/18/68)]and Ethics committee of All India Institute of Medical Sciences, New Delhi [Institute ethics committee (IEC), All India Institute of Medical Sciences (Ref No.: IEC-20/08.01.2021, RP-25/2021)] gave approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript.