Functional Seizures (FS)

Functional seizures (FS) are severely understudied paroxysmal episodes clinically similar to epileptic seizures but without aberrant brain electrical patterns.

FS is thought to be primarily related to psychiatric distress. FS patients have high rates of psychiatric comorbidities, and around 75% are female.

As part of this project, we developed an algorithm to characterize the clinical epidemiology of a FS patient population observed at Vanderbilt University Medical Center (VUMC; 0.14% prevalence). We corroborated previously reported associations, including post-traumatic stress disorder and sexual assault trauma, and identified novel associations, including cerebrovascular disease.

We hypothesize that FS is heritable and may share genetic architecture with epilepsy and dissociative disorders, both of which have significant snp- and twin- based heritability.

Using this validated algorithm, we are now conducting a multi-site FS GWAS meta-analysis, which is also the first FS GWAS reported to date.

Results currently include cases and controls identified from our BioVU samples, the Cleveland Clinic, BioMe, the Million Veterans Program, iPSYCH, and Massachusetts General BioBank. Our current sample size is n=9,289 cases and 417,818 controls. The sites used SAIGE, Bolt-LMM, and a inverse-weighted linear regression model in Plink, respectively to perform the analyses. All summary statistics are meta-analyzed using Metal.