Genetic Insights Into Neuromyelitis Optica Spectrum Disorder

ABSTRACT Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system characterized by recurrent inflammation, primarily targeting the optic nerves and spinal cord. The presence of anti‐aquaporin 4 antibodies has revealed core aspects of its immunopathology, but growing evidence suggests that genetic factors also contribute to individual susceptibility, clinical heterogeneity, and treatment response. Recent advances in genome‐wide association studies (GWAS), whole exome sequencing (WES), and Mendelian randomization (MR) have identified genetic variants associated with NMOSD. These findings span human leukocyte antigen (HLA) class II alleles, non‐HLA immune‐related genes, and somatic mutations acquired by clonal hematopoiesis. Importantly, genetic associations vary by ethnicity and may underlie the disparities seen in disease prevalence and phenotype. In addition, MR studies are revealing potential causal pathways involving immune mediators, cytokines, and metabolites, providing a new perspective on the disease mechanism. These genomic findings are accelerating our understanding of NMOSD and are expected to lead to risk stratification, refinement of diagnostic classification, and development of targeted therapies. This review provides an integrated overview of current genetic research in NMOSD and identifies implications for future precision medicine.