| dc.description.abstract | Functional seizures (FS), paroxysmal episodes that present like epileptic seizures but display no aberrant brain electrical patterns, are understudied. Patients have few treatment modalities and a high rate of comorbidities.
Our objective was to characterize the clinical and genetic epidemiology of a population of patients with FS observed at Vanderbilt University Medical Center (VUMC). We developed and validated an automated algorithm to identify FS patients in the VUMC electronic health record (VUMC-EHR) system. This resulted in the identification of 1,431 FS patients and 502,200 control patients with EHR records. Using BioVU, we had access to the genotypes of 309 FS patients and 59,856 controls. We conducted a GWAS meta-analysis using this data in combination with FS GWAS from five other sites, resulting in 9,028 FS cases and 561,432 controls for genetic analysis. Based on the GWAS, we then determined associated variants, genes, and the SNP-based heritability of FS.
Our clinical assessment replicated previously reported associations with psychiatric disorders including posttraumatic stress disorder (PTSD) (OR=1.22; 95% CI=1.21-1.24; P<3.02E−5) and anxiety (OR=1.14; 95% CI=1.13- 1.15; P<3.02E−5) and identified novel associations with cerebrovascular disease (OR=1.08; 95% CI=1.06-1.09; P<3.02E−5). An association was found between FS and the known risk factor sexual assault trauma (OR=10.26; 95% CI=10.09-10.44; P<3.02E-5), which we found to mediate nearly a quarter of the association between female sex and FS in the VUMC-EHR. Our genetic studies identified significant heritability (2.2%) of FS, and 58 genes whose predicted expression is associated with FS.
This study discovered an association between cerebrovascular disease and FS and suggested that sexual assault trauma may be a mediating factor in the association between female sex and FS. We have conducted the first and only FS GWAS meta-analysis to date and are the first data to calculate the heritability of FS. We hope this and the gene expression results we discovered will power future investigation of the molecular biology of FS, with the goal of eventually identifying effective drug targets to treat FS. | |
