Bidirectional Mendelian Randomization analysis of the genetic association between neuromyelitis optica spectrum disorder and cortical structure

Background Observational studies have suggested an association between neuromyelitis optica spectrum disorder (NMOSD) and cortical structure, but the results have been inconsistent. Objective We used two-sample Mendelian randomization (MR) to assess the bidirectional causal relationship between NMOSD and cortical structure. Methods Publicly available research by Karol Estrada et al. provided the NMOSD data, which included 1244 control patients, 132 cases of AQP4-IgG seropositive NMOSD, and 83 cases of AQP4-IgG seronegative NMOSD. ENIGMA Consortium provided genome-wide association study (GWAS) data for cortical surface area (SAw/nw) and thickness (THw/nw) in 51,665 people with European ancestry. For MR, the primary analysis approach employed was the inverse-variance weighted (IVW) method. Sensitivity analyses were used to assess pleiotropy and heterogeneity. Results Significant associations were identified between specific cortical regions and NMOSD subtypes. For NMOSD as an outcome, significant results included associations with pericalcarine THw (p = 0.0047,beta =-0.003), pericalcarine THnw (p = 0.0070,beta=-0.002), and superior temporal THw (p = 0.0252,beta = 0.002). For NMOSD as an exposure, significant associations included rostral middle frontal SAw (p = 0.0126,beta = 6.907), rostral middle frontal THw (p = 0.0288, beta =-0.001), and inferior parietal SAw (p = 0.0186, beta = 4.572). Conclusion Our findings support a reciprocal causal link between cortical anatomy and NMOSD.Confirming these relationships and clarifying the underlying mechanisms will require more investigation.