IS (idiopathic scoliosis) is a common spinal condition occurring in otherwise completely healthy adolescents. The root cause of IS remains unclear. This systematic review will focus on an update of genetic factors and IS etiology. Though it is generally accepted that the condition is not due to a single gene effect, etiology studies continue looking for a root cause including genetic variants. Though susceptibility from multiple genetic components is plausible based on known family history data, the literature remains unclear regarding multifactorial genetic influences. The objective of this study was to critically evaluate the evidence behind genetic causes (not single gene) of IS through a systematic review and strength-of-study analysis of existing genetic and genome-wide association studies (GWAS). We used the protocol of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).