Genetic variants associated with the occurrence and progression of adolescent idiopathic scoliosis: a systematic review protocol

Abstract

Abstract Background Adolescent idiopathic scoliosis (AIS) is a structural lateral spinal curvature of ≥ 10° with rotation. Approximately 2–3% of children in most populations are affected with AIS, and this condition is responsible for approximately $1.1 billion in surgical costs to the US healthcare system. Although a genetic factor for AIS has been demonstrated for decades, with multiple potentially contributory loci identified across populations, treatment options have remained limited to bracing and surgery. Methods The databases MEDLINE (via PubMed), Embase, Google Scholar, and Ovid MEDLINE will be searched and limited to articles in English. We will conduct title and abstract, full-text, and data extraction screening through Covidence, followed by data transfer to a custom REDCap database. Quality assessment will be confirmed by multiple reviewers. Studies containing variant-level data (i.e., GWAS, exome sequencing) for AIS subjects and controls will be considered. Outcomes of interest will include presence/absence of AIS, scoliosis curve severity, scoliosis curve progression, and presence/absence of nucleotide-level variants. Analyses will include odds ratios and relative risk assessments, and subgroup analysis (i.e., males vs. females, age groups) may be applied. Quality assessment tools will include GRADE and Q-Genie for genetic studies. Discussion In this systematic review, we seek to evaluate the quality of genetic evidence for AIS to better inform research efforts, to ultimately improve the quality of patient care and diagnosis. Systematic review registration PROSPERO registration #CRD42021243253

Keywords

• Adolescent idiopathic scoliosis (AIS)
• Genetic studies
• Genome-wide association
• Exome sequencing
• Whole genome sequencing
• Targeted sequencing