Association between genetic polymorphisms and risk of adolescent idiopathic scoliosis in case-control studies: a systematic review

Background Adolescent idiopathic scoliosis (AIS) is a structural lateral spinal curvature of >= 10 degrees with rotation. Approximately 2%-3% of children across populations are affected with AIS, and this condition is responsible for similar to$3 billion in costs within the USA. Although AIS is believed to have a strong genetic contribution, clinical translation of identified genetic variants has stalled. Methods The databases MEDLINE (via PubMed), Embase, Google Scholar and Ovid MEDLINE were searched and limited to articles in English. Title and abstract, full -text and data extraction screening was conducted through Covidence, followed by data transfer to a custom REDCap database. Studies containing variant- level data using genome- wide methodology as well as validation studies of genome- wide methods were considered. Quality assessment was conducted using Q-Genie. Results 33 studies were included, including 9 genome-wide association studies, 4 whole exome sequencing and 20 validation studies. Combined, these studies included data from >35,000 cases and >67,000 controls, not including validation cohorts. Additionally, results from six meta- analyses containing novel cohorts were also reported. All included study cohorts were from populations of primarily East Asian or Caucasian descent. Quality assessment found that overall study quality was high and control group selection was moderate. The highest number of reported associations were in single nucleotide polymorphisms (SNPs) in or near LBX1, LBX1-AS1, GPR126/ADGRG6 or BNC2. Conclusion AIS risk may be influenced by specific SNPs, particularly those in/near LBX1 and GPR126. Translatability of study findings is unknown due to an underrepresentation of most ethnic groups as well as few identified genome-wide studies. Further studies may benefit from increased cohort diversity and thorough evaluation of control cohort groups.