Authors :
Presenting Author: Marissa Kellogg, MD, MPH, FAES – Portland VA HCS & Oregon Health & Science Univ (OHSU)
Julie Lynch, PhD, RN, MBA – Salt Lake City VA HCS & Univ of Utah
Tia Dinatale, MPH – Salt Lake City VA HCS
Alica Goldman, MD, PhD – Baylor University
Elizabeth Gerard, MD – Northwestern University
Yi Li, MD, PhD – Stanford University
Matthew McCaskill, DO, MFA – Portland VA & Oregon Health & Science University (OHSU)
Colin Ellis, MD – University of Pennsylvania
Andrea Hildebrand, MS – Portland VA & OHSU
Jessica Minnier, PhD – OHSU & Portland VA
Nishant Mishra, MD, PhD – Yale University & West Haven VA HCS
Craig Teerlink, PhD – Salt Lake City VA HCS & Univ of Utah
Rationale:
Pathogenic variants in the SCN1A gene are a well-recognized cause of Dravet Syndrome, GEFS+, and febrile seizures. They can have variable expressivity and are rarely found in asymptomatic individuals. In this pilot study, we used the Veteran Health Administration (VHA) Million Veteran Program (MVP) genetic research biobank to explore the relationship between rare SCN1A single nucleotide variants (SNVs) and epilepsy prevalence in Veterans.
Methods:
Among MVP participants with whole genome sequencing (WGS) data, we extracted counts of all SNVs with minor allele frequency (MAF) < 0.01 within 10-Kb of the SCN1A gene. Variants were run through ANNOVAR to determine their ClinVar germline classification, which was used to group variants into pathogenicity categories (e.g. pathogenic, variants of uncertain significance [VUS], benign, etc.). We calculated odds ratios (OR) of epilepsy (as defined by a validated VHA algorithm for epilepsy) in MVP participants carrying different classifications of variants compared with the rest of the cohort (Fisher’s exact test).