Abstract TP6: Identification of Circulating Epigenetic Biomarkers for Seizure in Brain Arteriovenous Malformation by Methylome Profiling

Background: Brain arteriovenous malformations (bAVMs) are an important cause of intracranial hemorrhage, seizure, or other neurological deficits. Clinical heterogeneity of bAVM suggests a role for genetic modifiers that may associate with seizure risk. DNA methylation is a reversible epigenetic mechanism that regulates gene expression in development and disease. We hypothesized that DNA methylation in epilepsy-related genes is associated with seizure at presentation in bAVM patients. Methods: We performed a literature review in PubMed to identify epilepsy-related genes with potential epigenetic regulation using the search terms: epigenetics, DNA methylation, seizure, epilepsy. We selected 19 unruptured bAVM cases (mean age 44.9 y) enrolled in the bAVM study at UCSF, including 10 presenting with seizure. We performed methylome sequencing of genomic DNA extracted from whole blood using bisulfite sequencing services at Psomagen with ~20X coverage. Differentially Methylated Regions (DMR) mapping to or nearby the candidate seizure genes were identified by comparing the average methylation ratio in bAVM cases presenting with and without seizure by t-test. DMRs with a delta average methylation ratio between the two groups ≥