Causal Inference for Scoliosis and Strabismus: A 2-sample Mendelian Randomization Study

Abstract

Background: Some studies have shown an association between spinal curvature and strabismus, but the genetic association has not been clarified. Therefore, the present study is proposed to be a Mendelian randomization study aiming to investigate the genetic causal association between spinal curvature and strabismus. Purpose: Genetic causal associations between strabismus, convergent concomitant strabismus (Ccs), Divergent concomitant strabismus (Dcs), Other specified and unspecified strabismus (Osus), Other strabismus (Os) and spinal curvature were investigated by a bidirectionalMendelian randomization study to provide a basis for the prevention and treatment of spinal curvature. Methods: Significant and independent Single Nucleotide Polymorphisms (SNPs) in genome-wide association studies were selected as Instrumental Variables (IVs) for Mendelian Randomization (MR) analysis. Inverse Variance Weighted (IVW), MR-Egger regression, Weighted Median (WME), Simple Mode (SM), and weighted mode (WM) were used to analyze causal association; Heterogeneity and multiplicity tests were also performed and analyzed using the leave-one-out method to assess the stability of the results. Results: MR and reverse MR were utilized to assess the impact of scoliosis on strabismus, revealing that the 95% confidence intervals of all instrumental variables’ OR values spanned 1 and the p values were all above 0.05. These results indicate a lack of evidence supporting a causal relationship between scoliosis and strabismus. Conclusion: There is currently no conclusive evidence of a genetic causal relationship between scoliosis and strabismus, including their subtypes. Further laboratory studies are needed to confirm these findings, and future research with larger sample sizes is necessary to provide more robust support.