| Summary: | We performed a genome-wide association study (GWAS) to identify genetic variation associated with common forms of idiopathic generalized epilepsy (GE) and focal epilepsy (FE). Using a cohort of 2220 patients and 14,448 controls, we searched for single nucleotide polymorphisms (SNPs) associated with GE, FE and both forms combined. We did not find any SNPs that reached genome-wide statistical significance (<i>p</i> ≤ 5 × 10<sup>−8</sup>) when comparing all cases to all controls, and few SNPs of interest comparing FE cases to controls. However, we document multiple linked SNPs in the <i>PADI6</i>-<i>PADI4</i> genes that reach genome-wide significance and are associated with disease when comparing GE cases alone to controls. <i>PADI</i> genes encode enzymes that deiminate arginine to citrulline in molecular pathways related to epigenetic regulation of histones and autoantibody formation. Although epilepsy genetics and treatment are focused strongly on ion channel and neurotransmitter mechanisms, these results suggest that epigenetic control of gene expression and the formation of autoantibodies may also play roles in epileptogenesis.
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