K-H Yu1, N Palmer1, K Fox2, L Prock3, K D Mandl1,4, I S Kohane1,4, D Prilutsky4. 1. Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA. 2. Aetna Inc., Hartford, Connecticut, USA. 3. Division of Developmental Medicine, Boston Children's Hospital, Boston, Massachusetts, USA. 4. Computational Health Informatics Program, Boston Children's Hospital, Boston, Massachusetts, USA.
Abstract
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.
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 FXSpatients 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 FXSpatients 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 FXSpatients. 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 FXSpatients and their relevance to the FMR1 gene.
Authors: Chenyue Lu; Di Jin; Nathan Palmer; Kathe Fox; Isaac S Kohane; Jordan W Smoller; Kun-Hsing Yu Journal: Transl Psychiatry Date: 2022-04-11 Impact factor: 6.222