The phenotypical implications of immune dysregulation in fragile X syndrome

Background and purpose Immune system dysfunction and inflammatory dysregulation have been shown in several animal models of fragile X syndrome (FXS). However, the phenotypical implications of this dysregulation have not been systematically evaluated in a large patient cohort. Methods Five thousand seven hundred thirty‐six FXS patients from a nationwide health insurance database were identified and compared to 573 600 age‐ and sex‐matched controls. The phenome‐wide association studies codes of FXS patients and those without FXS were compared and the false discovery rate was controlled at 0.05 using the Benjamini–Hochberg procedure. Results In addition to the commonly reported comorbidities of FXS, an over‐representation of infectious diseases, including otitis media, cellulitis and abscess of fingers or toes, viral enteritis, candidiasis and pneumonia, was discovered. In addition, there was an under‐representation of autoimmune disorders in FXS patients. Conclusions Our systematic comorbidity analyses identified immunologically‐based phenotypes associated with FXS. Our findings align with previous observations of compromised immunity and phagocytic defects in animal models of FXS. These results suggest the importance of immune‐related pathways in FXS patients and their relevance to the FMR1 gene.