Genome Wide Association Study of Juvenile Idiopathic Epilepsy (JIE) in Egyptian Arabian Foals

Juvenile Idiopathic epilepsy (JIE) is a disorder in Egyptian Arabian foals that causes seizures during the first year of life. Potential life threatening complications include head injury and aspiration pneumonia. The disorder is heritable but the genetic mutation is unknown. The aim of this study was to identify single nucleotide polymorphism (SNP) markers significantly associated with the JIE phenotype. A genome wide association study using the Axiom^® Equine genotyping array with 670,000 SNP markers was performed on 48 Egyptian Arabian foal samples. JIE-affected foals (n=9) included foals with electroencephalographic (EEG) evidence of seizure activity, JIE-suspect foals (n=6) included foals with reported seizure activity by the owner but not confirmed by EEG and unaffected horses (n=33) included Egyptian Arabian horses over the age of 1 year with no history of juvenile seizures. A genome-wide efficient mixed model program (GEMMA) with sex as a covariate was used to analyze the data based on an elevated genomic inflation (λ=1.49) in the population, after excluding suspect foals (n=6) and obligate carriers (n=4) from the original sampling. Genome-wide significance was determined using a Bonferroni correction on the 445843 SNPs passing quality control. Population stratification was minimized using GEMMA analysis (λ=1.04) Two SNPs were identified on chromosome 1 (p=2.383932 and p=5.908369). This region is currently being prioritized for underlying putative functional variants in two JIE affected horses that have undergone whole genome sequencing.