TY - JOUR
T1 - Genetic variation in PADI6-PADI4 on 1p36.13 is associated with common forms of human generalized epilepsy
AU - Buono, Russell J.
AU - Bradfield, Jonathan P.
AU - Wei, Zhi
AU - Sperling, Michael R.
AU - Dlugos, Dennis J.
AU - Privitera, Michael D.
AU - French, Jacqueline A.
AU - Lo, Warren
AU - Cossette, Patrick
AU - Schachter, Steven C.
AU - Basehore, Heather
AU - Lohoff, Falk W.
AU - Grant, Struan F.A.
AU - Ferraro, Thomas N.
AU - Hakonarson, Hakon
N1 - Funding Information:
Funding: This research was funded by NIH R01-NS49306-01 to RJB and NIH R01-NS064154-01 to RJB and HH. The APC was funded by RJB using funds from the Camden Health Research Initiative internal grants sponsored by Rowan University.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/9
Y1 - 2021/9
N2 - 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 (p ≤ 5 × 10−8) 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 PADI6-PADI4 genes that reach genome-wide significance and are associated with disease when comparing GE cases alone to controls. PADI 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.
AB - 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 (p ≤ 5 × 10−8) 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 PADI6-PADI4 genes that reach genome-wide significance and are associated with disease when comparing GE cases alone to controls. PADI 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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U2 - 10.3390/genes12091441
DO - 10.3390/genes12091441
M3 - Article
C2 - 34573423
AN - SCOPUS:85115623546
SN - 2073-4425
VL - 12
JO - Genes
JF - Genes
IS - 9
M1 - 1441
ER -